Intratumoral Microbiota in Tumor: Current Understandings and Future Perspectives

Abstract

Intratumoral bacteria are increasingly recognized as integral and dynamic components of the tumor microenvironment (TME), with profound implications for tumor initiation, progression, metastasis, immune remodeling, and therapeutic response. These microorganisms may originate from mucosal barrier breaches, hematogenous or lymphatic dissemination, local migration from adjacent tissues, or co-migration with metastatic cells, and can be characterized by sequencing-based, imaging, culture-dependent, and multi-omics approaches. Accumulating evidence indicates that intratumoral bacteria contribute to tumorigenesis by inducing genomic instability, DNA damage, epigenetic alterations, oncogenic signaling, and chronic inflammation. Beyond primary tumor growth, they participate in multiple steps of the metastatic cascade, including epithelial–mesenchymal transition, cytoskeletal remodeling, invasion, intravasation, extravasation, pre-metastatic niche formation, angiogenesis, and distant colonization. Intratumoral bacteria also reshape immune and non-immune compartments of the TME, exerting dual effects by promoting immune suppression or enhancing antitumor immunity depending on bacterial species, tumor context, and host immune status. In this review, we summarize the historical development, methodological advances, cancer-type-specific diversity, and mechanistic roles of intratumoral microbiota in tumor progression and metastasis. We further discuss their diagnostic and prognostic value, as well as their therapeutic implications for conventional anticancer treatments and microbiota-targeted strategies, highlighting opportunities and challenges for microbiota-guided precision oncology.

Keywords

immune modulation / intratumoral bacteria / tumor metastasis / tumor microenvironment / tumor precision therapy

References

[1] D. Nejman, I. Livyatan, G. Fuks, et al., “The Human Tumor Microbiome Is Composed of Tumor Type-Specific Intracellular Bacteria,” Science 368, no. 6494 (2020): 973–980.

[2] L. Narunsky-Haziza, G. D. Sepich-Poore, I. Livyatan, et al., “Pan-Cancer Analyses Reveal Cancer-Type-Specific Fungal Ecologies and Bacteriome Interactions,” Cell 185, no. 20 (2022): 3789–3806.e17.

[3] A. B. Dohlman, J. Klug, M. Mesko, et al., “A Pan-Cancer Mycobiome Analysis Reveals Fungal Involvement in Gastrointestinal and Lung Tumors,” Cell 185, no. 20 (2022): 3807–3822.e12.

[4] Y. He, Q. Zhang, X. Yu, S. Zhang, and W. Guo, “Overview of Microbial Profiles in human Hepatocellular Carcinoma and Adjacent Nontumor Tissues,” Journal of Translational Medicine 21, no. 1 (2023): 68.

[5] Z. Shi, H. Ren, C. Lin, et al., “Tissue-Resident Microbiota Impacts Colorectal Cancer Progression and Prognosis,” Nature Communications 17, no. 1 (2025): 346.

[6] Y. Cao, H. Xia, X. Tan, et al., “Intratumoural Microbiota: A New Frontier in Cancer Development and Therapy,” Signal Transduction and Targeted Therapy 9, no. 1 (2024): 15.

[7] L. Yang, A. Li, Y. Wang, and Y. Zhang, “Intratumoral Microbiota: Roles in Cancer Initiation, Development and Therapeutic Efficacy,” Signal Transduction and Targeted Therapy 8, no. 1 (2023): 35.

[8] C. Xue, X. Gu, Q. Shi, et al., “The Interaction Between Intratumoral Bacteria and Metabolic Distortion in Hepatocellular Carcinoma,” Journal of Translational Medicine 22, no. 1 (2024): 237.

[9] A. W. Lambert, Y. Zhang, and R. A. Weinberg, “Cell-Intrinsic and Microenvironmental Determinants of Metastatic Colonization,” Nature Cell Biology 26, no. 5 (2024): 687–697.

[10] K. Ganesh and J. Massagué, “Targeting Metastatic Cancer,” Nature Medicine 27, no. 1 (2021): 34–44.

[11] S. Gerstberger, Q. Jiang, and K. Ganesh, “Metastasis,” Cell 186, no. 8 (2023): 1564–1579.

[12] R. L. Siegel, T. B. Kratzer, N. S. Wagle, H. Sung, and A. Jemal, “Cancer Statistics, 2026,” CA: A Cancer Journal for Clinicians 76, no. 1 (2026): e70043.

[13] K. Mani, D. Deng, C. Lin, M. Wang, M. L. Hsu, and N. G. Zaorsky, “Causes of Death Among People Living With Metastatic Cancer,” Nature Communications 15, no. 1 (2024): 1519.

[14] C. Xue, Q. Chu, Q. Zheng, et al., “Current Understanding of the Intratumoral Microbiome in Various Tumors,” Cell Reports Medicine 4, no. 1 (2023): 100884.

[15] H. Zhang, L. Fu, X. Leiliang, et al., “Beyond the Gut: The Intratumoral Microbiome's Influence on Tumorigenesis and Treatment Response,” Cancer Communications 44, no. 10 (2024): 1130–1167.

[16] A. Fu, B. Yao, T. Dong, and S. Cai, “Emerging Roles of Intratumor Microbiota in Cancer Metastasis,” Trends in Cell Biology 33, no. 7 (2023): 583–593.

[17] C. Kong, X. Yan, Y. Zhu, et al., “Fusobacterium Nucleatum Promotes the Development of Colorectal Cancer by Activating a Cytochrome P450/Epoxyoctadecenoic Acid Axis via TLR4/Keap1/NRF2 Signaling,” Cancer Research 81, no. 17 (2021): 4485–4498.

[18] D. Mouradov, P. Greenfield, S. Li, et al., “Oncomicrobial Community Profiling Identifies Clinicomolecular and Prognostic Subtypes of Colorectal Cancer,” Gastroenterology 165, no. 1 (2023): 104–120.

[19] S. Okuda, Y. Shimada, Y. Tajima, et al., “Profiling of Host Genetic Alterations and Intra-Tumor Microbiomes in Colorectal Cancer,” Computational and Structural Biotechnology Journal 19 (2021): 3330–3338.

[20] F. Peng, M. Hu, Z. Su, L. Hu, L. Guo, and K. Yang, “Intratumoral Microbiota as a Target for Advanced Cancer Therapeutics,” Advanced Materials 36, no. 38 (2024): e2405331.

[21] Z. Shi, Z. Li, and M. Zhang, “Emerging Roles of Intratumor Microbiota in Cancer: Tumorigenesis and Management Strategies,” Journal of Translational Medicine 22, no. 1 (2024): 837.

[22] G. D. Sepich-Poore, L. Zitvogel, R. Straussman, J. Hasty, J. A. Wargo, and R. Knight, “The Microbiome and Human Cancer,” Science 371, no. 6536 (2021): eabc4552.

[23] S. J. Salter, M. J. Cox, E. M. Turek, et al., “Reagent and Laboratory Contamination Can Critically Impact Sequence-Based Microbiome Analyses,” BMC Biology 12 (2014): 87.

[24] R. Eisenhofer, J. J. Minich, C. Marotz, A. Cooper, R. Knight, and L. S. Weyrich, “Contamination in Low Microbial Biomass Microbiome Studies: Issues and Recommendations,” Trends in Microbiology 27, no. 2 (2019): 105–117.

[25] A. Gihawi, Y. Ge, J. Lu, et al., “Major Data Analysis Errors Invalidate Cancer Microbiome Findings,” MBio 14, no. 5 (2023): e0160723.

[26] B. Wiemann and C. O. Starnes, “Coley's Toxins, Tumor Necrosis Factor and Cancer Research: A Historical Perspective,” Pharmacology & Therapeutics 64, no. 3 (1994): 529–564.

[27] S. A. Hoption Cann, J. P. van Netten, and C. van Netten, “Dr William Coley and Tumour Regression: A Place in History or in the Future,” Postgraduate Medical Journal 79, no. 938 (2003): 672–680.

[28] P. Rous, “A Sarcoma of the Fowl Transmissible by an Agent Separable from the Tumor Cells,” Journal of Experimental Medicine 13, no. 4 (1911): 397–411.

[29] M. A. Epstein, B. G. Achong, and Y. M. Barr, “Virus Particles in Cultured Lymphoblasts from Burkitt's Lymphoma,” Lancet 1, no. 7335 (1964): 702–703.

[30] J. R. Warren and B. Marshall, “Unidentified Curved Bacilli on Gastric Epithelium in Active Chronic Gastritis,” Lancet 1, no. 8336 (1983): 1273–1275.

[31] W. Fischbach and P. Malfertheiner, “Helicobacter pylori Infection,” Deutsches Arzteblatt International 115, no. 25 (2018): 429–436.

[32] T. W. Battaglia, I. L. Mimpen, J. J. H. Traets, et al., “A Pan-Cancer Analysis of the Microbiome in Metastatic Cancer,” Cell 187, no. 9 (2024): 2324–2335, e19.

[33] J. L. Galeano Niño, H. Wu, and K. D. LaCourse, “Effect of the Intratumoral Microbiota on Spatial and Cellular Heterogeneity in Cancer,” Nature 611, no. 7937 (2022): 810–817.

[34] S. Saarenpää, O. Shalev, H. Ashkenazy, et al., “Spatial Metatranscriptomics Resolves Host-Bacteria-Fungi Interactomes,” Nature Biotechnology 42, no. 9 (2024): 1384–1393.

[35] W. Zhou, Q. Yang, J. Guo, et al., “SMTdb: A Comprehensive Spatial Meta-Transcriptome Resource in Cancer,” Molecular Biology and Evolution 42, no. 11 (2025): msaf263.

[36] J. B. Patel, “16S rRNA Gene Sequencing for Bacterial Pathogen Identification in the Clinical Laboratory,” Molecular Diagnosis 6, no. 4 (2001): 313–321.

[37] P. Yarza, P. Yilmaz, E. Pruesse, et al., “Uniting the Classification of Cultured and Uncultured Bacteria and Archaea Using 16S rRNA Gene Sequences,” Nature Reviews Microbiology 12, no. 9 (2014): 635–645.

[38] C. Quince, A. W. Walker, J. T. Simpson, N. J. Loman, and N. Segata, “Corrigendum: Shotgun Metagenomics, From Sampling to Analysis,” Nature Biotechnology 35, no. 12 (2017): 1211.

[39] A. Mukherjee and M. S. Reddy, “Metatranscriptomics: An Approach for Retrieving Novel Eukaryotic Genes From Polluted and Related Environments,” 3 Biotech 10, no. 2 (2020): 71.

[40] Y. Xie, F. Xie, X. Zhou, et al., “Microbiota in Tumors: From Understanding to Application,” Advanced Science 9, no. 21 (2022): e2200470.

[41] A. E. Budding, M. E. Grasman, F. Lin, et al., “IS-pro: High-Throughput Molecular Fingerprinting of the Intestinal Microbiota,” FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology 24, no. 11 (2010): 4556–4564.

[42] C. J. F. Heymann, J. M. Bard, M. F. Heymann, D. Heymann, and C. Bobin-Dubigeon, “The Intratumoral Microbiome: Characterization Methods and Functional Impact,” Cancer Letters 522 (2021): 63–79.

[43] A. D. Kostic, D. Gevers, C. S. Pedamallu, et al., “Genomic Analysis Identifies Association of Fusobacterium With Colorectal Carcinoma,” Genome Research 22, no. 2 (2012): 292–298.

[44] I. Pope, H. Tanner, F. Masia, et al., “Correlative Light-Electron Microscopy Using Small Gold Nanoparticles as Single Probes,” Light, Science & Applications 12, no. 1 (2023): 80.

[45] Z. Huang, S. Mo, L. Yan, et al., “A Simple Culture Method Enhances the Recovery of Culturable Actinobacteria from Coastal Sediments,” Frontiers in Microbiology 12 (2021): 675048.

[46] W. H. Lewis, G. Tahon, P. Geesink, D. Z. Sousa, and T. J. G. Ettema, “Innovations to Culturing the Uncultured Microbial Majority,” Nature Reviews Microbiology 19, no. 4 (2021): 225–240.

[47] E. Gigi, N. Gavert, L. Raijman-Nagar, et al., “Characterization of the Tumor Microbiome of Brain Metastases and Glioblastoma Reveals Tumor-Type-Specific and Location-Specific Microbial Signatures,” Nature Cancer 6, no. 11 (2025): 1761–1776.

[48] X. Qian, H. Y. Zhang, Q. L. Li, et al., “Integrated Microbiome, Metabolome, and Proteome Analysis Identifies a Novel Interplay Among Commensal Bacteria, Metabolites and Candidate Targets in Non-Small Cell Lung Cancer,” Clinical and Translational Medicine 12, no. 6 (2022): e947.

[49] R. A. Alharbi, “Proteomics Approach and Techniques in Identification of Reliable Biomarkers for Diseases,” Saudi Journal of Biological Sciences 27, no. 3 (2020): 968–974.

[50] E. B. Daliri, S. Wei, D. H. Oh, and B. H. Lee, “The Human Microbiome and Metabolomics: Current Concepts and Applications,” Critical Reviews in Food Science and Nutrition 57, no. 16 (2017): 3565–3576.

[51] A. Fu, B. Yao, T. Dong, et al., “Tumor-Resident Intracellular Microbiota Promotes Metastatic Colonization in Breast Cancer,” Cell 185, no. 8 (2022): 1356–1372, e26.

[52] W. Liu, X. Zhang, H. Xu, et al., “Microbial Community Heterogeneity Within Colorectal Neoplasia and Its Correlation with Colorectal Carcinogenesis,” Gastroenterology 160, no. 7 (2021): 2395–2408.

[53] J. S. Johnson, D. J. Spakowicz, B. Y. Hong, et al., “Evaluation of 16S rRNA Gene Sequencing for Species and Strain-Level Microbiome Analysis,” Nature Communications 10, no. 1 (2019): 5029.

[54] J. E. Clarridge 3rd, “Impact of 16S rRNA Gene Sequence Analysis for Identification of Bacteria on Clinical Microbiology and Infectious Diseases,” Clinical Microbiology Reviews 17, no. 4 (2004): 840–862.

[55] X. Zhou, S. Kandalai, F. Hossain, and Q. Zheng, “Tumor Microbiome Metabolism: A Game Changer in Cancer Development and Therapy,” Frontiers in Oncology 12 (2022): 933407.

[56] N. Zhang, S. Kandalai, X. Zhou, F. Hossain, and Q. Zheng, “Applying Multi-Omics Toward Tumor Microbiome Research,” iMeta 2, no. 1 (2023): e73.

[57] S. Zaki, D. M. Blau, J. M. Hughes, et al., “CDC Grand Rounds: Discovering New Diseases via Enhanced Partnership Between Public Health and Pathology Experts,” MMWR Morbidity and Mortality Weekly Report 63, no. 6 (2014): 121–126.

[58] X. Chai, J. Wang, H. Li, et al., “Intratumor Microbiome Features Reveal Antitumor Potentials of Intrahepatic Cholangiocarcinoma,” Gut Microbes 15, no. 1 (2023): 2156255.

[59] K. L. Cross, J. H. Campbell, M. Balachandran, et al., “Targeted Isolation and Cultivation of Uncultivated Bacteria by Reverse Genomics,” Nature Biotechnology 37, no. 11 (2019): 1314–1321.

[60] J. Puschhof, C. Pleguezuelos-Manzano, A. Martinez-Silgado, et al., “Intestinal Organoid Cocultures With Microbes,” Nature Protocols 16, no. 10 (2021): 4633–4649.

[61] R. J. Thompson, H. G. Bouwer, D. A. Portnoy, and F. R. Frankel, “Pathogenicity and Immunogenicity of a Listeria monocytogenes Strain That Requires D-Alanine for Growth,” Infection and Immunity 66, no. 8 (1998): 3552–3561.

[62] S. M. Desmarais, M. A. De Pedro, F. Cava, and K. C. Huang, “Peptidoglycan at Its Peaks: How Chromatographic Analyses Can Reveal Bacterial Cell Wall Structure and Assembly,” Molecular Microbiology 89, no. 1 (2013): 1–13.

[63] Y. Q. Lu, H. Qiao, X. R. Tan, and N. Liu, “Broadening Oncological Boundaries: The Intratumoral Microbiota,” Trends in Microbiology 32, no. 8 (2024): 807–822.

[64] Y. Ge, J. Lu, D. Puiu, M. Revsine, and S. L. Salzberg, “Comprehensive Analysis of Microbial Content in Whole-Genome Sequencing Samples From the Cancer Genome Atlas Project,” Science Translational Medicine 17, no. 814 (2025): eads6335.

[65] A. Gihawi, H. M. Wood, J. Clark, et al., “The Landscape of Microbial Associations in human Cancer,” Science Translational Medicine 17, no. 814 (2025): eads6166.

[66] I. Cho and M. J. Blaser, “The human Microbiome: At the Interface of Health and Disease,” Nature Reviews Genetics 13, no. 4 (2012): 260–270.

[67] R. V. Purcell, J. Pearson, A. Aitchison, L. Dixon, F. A. Frizelle, and J. I. Keenan, “Colonization With Enterotoxigenic Bacteroides fragilis Is Associated With Early-Stage Colorectal Neoplasia,” PLoS ONE 12, no. 2 (2017): e0171602.

[68] S. Yamamoto, H. Kinugasa, M. Hirai, et al., “Heterogeneous Distribution of Fusobacterium nucleatum in the Progression of Colorectal Cancer,” Journal of Gastroenterology and Hepatology 36, no. 7 (2021): 1869–1876.

[69] Z. Lin, W. Rao, Z. Xiang, et al., “Characteristics and Interplay of Esophageal Microbiota in Esophageal Squamous Cell Carcinoma,” BMC Cancer 22, no. 1 (2022): 696.

[70] B. A. Peters, R. B. Hayes, C. Goparaju, C. Reid, H. I. Pass, and J. Ahn, “The Microbiome in Lung Cancer Tissue and Recurrence-Free Survival,” Cancer Epidemiology, Biomarkers & Prevention 28, no. 4 (2019): 731–740.

[71] J. Abed, J. E. Emgård, G. Zamir, et al., “Fap2 Mediates Fusobacterium nucleatum Colorectal Adenocarcinoma Enrichment by Binding to Tumor-Expressed Gal-GalNAc,” Cell Host & Microbe 20, no. 2 (2016): 215–225.

[72] L. Parhi, T. Alon-Maimon, and A. Sol, “Breast Cancer Colonization by Fusobacterium nucleatum Accelerates Tumor Growth and Metastatic Progression,” Nature Communications 11, no. 1 (2020): 3259.

[73] C. L. Murphy, M. Barrett, P. Pellanda, et al., “Mapping the Colorectal Tumor Microbiota,” Gut Microbes 13, no. 1 (2021): 1–10.

[74] S. Bullman, C. S. Pedamallu, E. Sicinska, et al., “Analysis of Fusobacterium Persistence and Antibiotic Response in Colorectal Cancer,” Science 358, no. 6369 (2017): 1443–1448.

[75] N. Agrawal, C. Bettegowda, I. Cheong, et al., “Bacteriolytic Therapy Can Generate a Potent Immune Response Against Experimental Tumors,” Proceedings of the National Academy of Sciences of the United States of America 101, no. 42 (2004): 15172–15177.

[76] R. W. Kasinskas and N. S. Forbes, “Salmonella Typhimurium Lacking Ribose Chemoreceptors Localize in Tumor Quiescence and Induce Apoptosis,” Cancer Research 67, no. 7 (2007): 3201–3209.

[77] N. S. Forbes, “Engineering the Perfect (Bacterial) Cancer Therapy,” Nature Reviews Cancer 10, no. 11 (2010): 785–794.

[78] X. Zhong, X. He, Y. Wang, et al., “Warburg Effect in Colorectal Cancer: The Emerging Roles in Tumor Microenvironment and Therapeutic Implications,” Journal of Hematology & Oncology 15, no. 1 (2022): 160.

[79] K. Yazawa, M. Fujimori, T. Nakamura, et al., “Bifidobacterium Longum as a Delivery System for Gene Therapy of Chemically Induced Rat Mammary Tumors,” Breast Cancer Research and Treatment 66, no. 2 (2001): 165–170.

[80] S. Pushalkar, M. Hundeyin, D. Daley, et al., “The Pancreatic Cancer Microbiome Promotes Oncogenesis by Induction of Innate and Adaptive Immune Suppression,” Cancer Discovery 8, no. 4 (2018): 403–416.

[81] B. Ghaddar, A. Biswas, C. Harris, et al., “Tumor Microbiome Links Cellular Programs and Immunity in Pancreatic Cancer,” Cancer Cell 40, no. 10 (2022): 1240–1253, e5.

[82] L. T. Geller, M. Barzily-Rokni, T. Danino, et al., “Potential Role of Intratumor Bacteria in Mediating Tumor Resistance to the Chemotherapeutic Drug Gemcitabine,” Science 357, no. 6356 (2017): 1156–1160.

[83] S. J. Taylor, M. G. Winter, C. C. Gillis, et al., “Colonocyte-derived Lactate Promotes E. coli Fitness in the Context of Inflammation-Associated Gut Microbiota Dysbiosis,” Microbiome 10, no. 1 (2022): 200.

[84] R. Holani, H. Bar-Yoseph, Z. Krekhno, et al., “Bile Acid-Induced Metabolic Changes in the Colon Promote Enterobacteriaceae Expansion and Associate With Dysbiosis in Crohn's Disease,” Science Signaling 17, no. 867 (2024): eadl1786.

[85] C. Clairmont, K. C. Lee, J. Pike, et al., “Biodistribution and Genetic Stability of the Novel Antitumor Agent VNP20009, a Genetically Modified Strain of Salmonella Typhimurium,” Journal of Infectious Diseases 181, no. 6 (2000): 1996–2002.

[86] N. L. Silver, J. Dai, T. D. Kerr, et al., “Intratumoral Bacteria Are Immunosuppressive and Promote Immunotherapy Resistance in Head and Neck Squamous Cell Carcinoma,” Nature Cancer 7, no. 1 (2026): 80–97.

[87] A. B. Dohlman, D. Arguijo Mendoza, S. Ding, et al., “The Cancer Microbiome Atlas: A Pan-Cancer Comparative Analysis to Distinguish Tissue-Resident Microbiota From Contaminants,” Cell Host & Microbe 29, no. 2 (2021): 281–298.e5.

[88] K. Mima, R. Nishihara, Z. R. Qian, et al., “Fusobacterium nucleatum in Colorectal Carcinoma Tissue and Patient Prognosis,” Gut 65, no. 12 (2016): 1973–1980.

[89] E. Riquelme, Y. Zhang, L. Zhang, et al., “Tumor Microbiome Diversity and Composition Influence Pancreatic Cancer Outcomes,” Cell 178, no. 4 (2019): 795–806.e12.

[90] M. R. Rubinstein, X. Wang, W. Liu, Y. Hao, G. Cai, and Y. W. Han, “Fusobacterium nucleatum Promotes Colorectal Carcinogenesis by Modulating E-Cadherin/β-Catenin Signaling via Its FadA Adhesin,” Cell Host & Microbe 14, no. 2 (2013): 195–206.

[91] T. Yu, F. Guo, Y. Yu, et al., “Fusobacterium nucleatum Promotes Chemoresistance to Colorectal Cancer by Modulating Autophagy,” Cell 170, no. 3 (2017): 548–563.e16.

[92] S. Zhang, J. Huang, Z. Jiang, H. Tong, X. Ma, and Y. Liu, “Tumor Microbiome: Roles in Tumor Initiation, Progression, and Therapy,” Molecular Biomedicine 6, no. 1 (2025): 9.

[93] C. Pleguezuelos-Manzano, J. Puschhof, A. Rosendahl Huber, et al., “Mutational Signature in Colorectal Cancer Caused by Genotoxic Pks(+) E. coli,” Nature 580, no. 7802 (2020): 269–273.

[94] J. P. Nougayrède, S. Homburg, F. Taieb, et al., “Escherichia coli Induces DNA Double-strand Breaks in Eukaryotic Cells,” Science 313, no. 5788 (2006): 848–851.

[95] J. C. Arthur, E. Perez-Chanona, M. Mühlbauer, et al., “Intestinal Inflammation Targets Cancer-Inducing Activity of the Microbiota,” Science 338, no. 6103 (2012): 120–123.

[96] Z. R. Li, J. Li, W. Cai, et al., “Macrocyclic Colibactin Induces DNA Double-Strand Breaks via Copper-Mediated Oxidative Cleavage,” Nature Chemistry 11, no. 10 (2019): 880–889.

[97] F. Geng, Y. Zhang, Z. Lu, S. Zhang, and Y. Pan, “Fusobacterium nucleatum Caused DNA Damage and Promoted Cell Proliferation by the Ku70/p53 Pathway in Oral Cancer Cells,” DNA and Cell Biology 39, no. 1 (2020): 144–151.

[98] A. Boleij, E. M. Hechenbleikner, A. C. Goodwin, et al., “The Bacteroides fragilis Toxin Gene Is Prevalent in the Colon Mucosa of Colorectal Cancer Patients,” Clinical Infectious Diseases 60, no. 2 (2015): 208–215.

[99] Z. He, R. Z. Gharaibeh, R. C. Newsome, et al., “Campylobacter jejuni Promotes Colorectal Tumorigenesis Through the Action of Cytolethal Distending Toxin,” Gut 68, no. 2 (2019): 289–300.

[100] A. C. Goodwin, C. E. Destefano Shields, and S. Wu, “Polyamine Catabolism Contributes to Enterotoxigenic Bacteroides fragilis-Induced Colon Tumorigenesis,” Proceedings of the National Academy of Sciences of the United States of America 108, no. 37 (2011): 15354–15359.

[101] C. C. Wong and J. Yu, “Gut Microbiota in Colorectal Cancer Development and Therapy,” Nature Reviews Clinical Oncology 20, no. 7 (2023): 429–452.

[102] C. Xue, J. Jia, X. Gu, et al., “Intratumoral Bacteria Interact With Metabolites and Genetic Alterations in Hepatocellular Carcinoma,” Signal Transduction and Targeted Therapy 7, no. 1 (2022): 335.

[103] H. E. Park, J. H. Kim, N. Y. Cho, H. S. Lee, and G. H. Kang, “Intratumoral Fusobacterium nucleatum Abundance Correlates With Macrophage Infiltration and CDKN2A Methylation in Microsatellite-Unstable Colorectal Carcinoma,” Virchows Archiv: An International Journal of Pathology 471, no. 3 (2017): 329–336.

[104] P. H. Park, K. Keith, G. Calendo, et al., “Association Between Gut Microbiota and CpG Island Methylator Phenotype in Colorectal Cancer,” Gut Microbes 16, no. 1 (2024): 2363012.

[105] A. A. Vega, E. A. Marshall, A. J. C. Noonan, et al., “Methionine-Producing Tumor Micro(be) Environment Fuels Growth of Solid Tumors,” Cellular Oncology 46, no. 6 (2023): 1659–1673.

[106] S. Chen, L. Zhang, M. Li, et al., “Fusobacterium nucleatum Reduces METTL3-Mediated M(6)A Modification and Contributes to Colorectal Cancer Metastasis,” Nature Communications 13, no. 1 (2022): 1248.

[107] R. Lu, S. Wu, Y. G. Zhang, et al., “Enteric Bacterial Protein AvrA Promotes Colonic Tumorigenesis and Activates Colonic Beta-Catenin Signaling Pathway,” Oncogenesis 3, no. 6 (2014): e105.

[108] R. Lu, X. Liu, S. Wu, et al., “Consistent Activation of the β-Catenin Pathway by Salmonella Type—Three Secretion Effector Protein AvrA in Chronically Infected Intestine,” American Journal of Physiology Gastrointestinal and Liver Physiology 303, no. 10 (2012): G1113–G1125.

[109] G. Hoxhaj and B. D. Manning, “The PI3K-AKT Network at the Interface of Oncogenic Signalling and Cancer Metabolism,” Nature Reviews Cancer 20, no. 2 (2020): 74–88.

[110] F. Rascio, F. Spadaccino, M. T. Rocchetti, et al., “The Pathogenic Role of PI3K/AKT Pathway in Cancer Onset and Drug Resistance: An Updated Review,” Cancers 13, no. 16 (2021): 3949.

[111] M. Martini, M. C. De Santis, L. Braccini, F. Gulluni, and E. Hirsch, “PI3K/AKT Signaling Pathway and Cancer: An Updated Review,” Annals of Medicine 46, no. 6 (2014): 372–383.

[112] J. J. Tsay, B. G. Wu, M. H. Badri, et al., “Airway Microbiota Is Associated With Upregulation of the PI3K Pathway in Lung Cancer,” American Journal of Respiratory and Critical Care Medicine 198, no. 9 (2018): 1188–1198.

[113] I. Chattopadhyay, M. Verma, and M. Panda, “Role of Oral Microbiome Signatures in Diagnosis and Prognosis of Oral Cancer,” Technology in Cancer Research & Treatment 18 (2019): 1533033819867354.

[114] A. Martin-Vega and M. H. Cobb, “ERK1/2-MAPK Signaling: Metabolic, Organellar, and Cytoskeletal Interactions,” Current Opinion in Cell Biology 95 (2025): 102526.

[115] D. A. Fruman, H. Chiu, B. D. Hopkins, S. Bagrodia, L. C. Cantley, and R. T. Abraham, “The PI3K Pathway in Human Disease,” Cell 170, no. 4 (2017): 605–635.

[116] J. Gnanasekaran, A. Binder Gallimidi, and E. Saba, “Intracellular Porphyromonas gingivalis Promotes the Tumorigenic Behavior of Pancreatic Carcinoma Cells,” Cancers 12, no. 8 (2020): 2331.

[117] W. Mu, Y. Jia, X. Chen, H. Li, Z. Wang, and B. Cheng, “Intracellular Porphyromonas gingivalis Promotes the Proliferation of Colorectal Cancer Cells via the MAPK/ERK Signaling Pathway,” Frontiers in Cellular and Infection Microbiology 10 (2020): 584798.

[118] G. N. Barber, “STING: Infection, Inflammation and Cancer,” Nature Reviews Immunology 15, no. 12 (2015): 760–770.

[119] Y. Shi, W. Zheng, K. Yang, et al., “Intratumoral Accumulation of Gut Microbiota Facilitates CD47-Based Immunotherapy via STING Signaling,” Journal of Experimental Medicine 217, no. 5 (2020): e20192282.

[120] H. Zhao, L. Wu, G. Yan, et al., “Inflammation and Tumor Progression: Signaling Pathways and Targeted Intervention,” Signal Transduction and Targeted Therapy 6, no. 1 (2021): 263.

[121] T. Duan, Y. Du, C. Xing, H. Y. Wang, and R. F. Wang, “Toll-Like Receptor Signaling and Its Role in Cell-Mediated Immunity,” Frontiers in Immunology 13 (2022): 812774.

[122] Y. Yang, W. Weng, J. Peng, et al., “Fusobacterium nucleatum Increases Proliferation of Colorectal Cancer Cells and Tumor Development in Mice by Activating Toll-Like Receptor 4 Signaling to Nuclear Factor-κB, and Up-Regulating Expression of MicroRNA-21,” Gastroenterology 152, no. 4 (2017): 851–866.e24.

[123] S. Wu, K. C. Lim, J. Huang, R. F. Saidi, and C. L. Sears, “Bacteroides fragilis Enterotoxin Cleaves the Zonula Adherens Protein, E-Cadherin,” Proceedings of the National Academy of Sciences of the United States of America 95, no. 25 (1998): 14979–14984.

[124] L. Chung, E. Thiele Orberg, and A. L. Geis, “Bacteroides fragilis Toxin Coordinates a Pro-Carcinogenic Inflammatory Cascade via Targeting of Colonic Epithelial Cells,” Cell Host & Microbe 23, no. 2 (2018): 203–214, e5.

[125] A. Rivas-Domínguez, N. Pastor, L. Martínez-López, J. Colón-Pérez, B. Bermúdez, and M. L. Orta, “The Role of DNA Damage Response in Dysbiosis-Induced Colorectal Cancer,” Cells 10, no. 8 (2021): 1934.

[126] J. Katz, M. D. Onate, K. M. Pauley, I. Bhattacharyya, and S. Cha, “Presence of Porphyromonas gingivalis in Gingival Squamous Cell Carcinoma,” International Journal of Oral Science 3, no. 4 (2011): 209–215.

[127] M. Castaneda, P. den Hollander, N. A. Kuburich, J. M. Rosen, and S. A. Mani, “Mechanisms of Cancer Metastasis,” Seminars in Cancer Biology 87 (2022): 17–31.

[128] X. Guan, “Cancer Metastases: Challenges and Opportunities,” Acta Pharmaceutica Sinica B 5, no. 5 (2015): 402–418.

[129] Y. Huang, W. Hong, and X. Wei, “The Molecular Mechanisms and Therapeutic Strategies of EMT in Tumor Progression and Metastasis,” Journal of Hematology & Oncology 15, no. 1 (2022): 129.

[130] D. Hanahan and R. A. Weinberg, “Hallmarks of Cancer: The Next Generation,” Cell 144, no. 5 (2011): 646–674.

[131] Y. Wu, S. Guo, F. Chen, et al., “Fn-Dps, a Novel Virulence Factor of Fusobacterium nucleatum, Disrupts Erythrocytes and Promotes Metastasis in Colorectal Cancer,” PLoS Pathogens 19, no. 1 (2023): e1011096.

[132] M. Hayashi, N. Ikenaga, K. Nakata, et al., “Intratumor Fusobacterium nucleatum Promotes the Progression of Pancreatic Cancer via the CXCL1-CXCR2 Axis,” Cancer Science 114, no. 9 (2023): 3666–3678.

[133] S. Zhang, C. Li, J. Liu, et al., “Fusobacterium nucleatum Promotes Epithelial-Mesenchymal Transition Through Regulation of the lncRNA MIR4435-2HG/miR-296-5p/Akt2/SNAI1 Signaling Pathway,” FEBS Journal 287, no. 18 (2020): 4032–4047.

[134] G. Chen, C. Gao, S. Jiang, et al., “Fusobacterium nucleatum Outer Membrane Vesicles Activate Autophagy to Promote Oral Cancer Metastasis,” Journal of Advanced Research 56 (2024): 167–179.

[135] E. Bessède, C. Staedel, L. A. Acuña Amador, et al., “Helicobacter pylori Generates Cells With Cancer Stem Cell Properties via Epithelial-Mesenchymal Transition-Like Changes,” Oncogene 33, no. 32 (2014): 4123–4131.

[136] R. Roy, J. Yang, and M. A. Moses, “Matrix Metalloproteinases as Novel Biomarkers and Potential Therapeutic Targets in Human Cancer,” Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology 27, no. 31 (2009): 5287–5297.

[137] S. Ou, H. Chen, H. Wang, et al., “Fusobacterium nucleatum Upregulates MMP7 to Promote Metastasis-Related Characteristics of Colorectal Cancer Cell via Activating MAPK(JNK)-AP1 Axis,” Journal of Translational Medicine 21, no. 1 (2023): 704.

[138] P. J. Bergin, E. Anders, W. Sicheng, et al., “Increased Production of Matrix Metalloproteinases in Helicobacter pylori-Associated Human Gastritis,” Helicobacter 9, no. 3 (2004): 201–210.

[139] Y. Ma, H. Chen, H. Li, et al., “Intratumor Microbiome-Derived Butyrate Promotes Lung Cancer Metastasis,” Cell Reports Medicine 5, no. 4 (2024): 101488.

[140] S. Parida, S. Wu, S. Siddharth, et al., “A Procarcinogenic Colon Microbe Promotes Breast Tumorigenesis and Metastatic Progression and Concomitantly Activates Notch and β-Catenin Axes,” Cancer Discovery 11, no. 5 (2021): 1138–1157.

[141] Z. He, J. Yu, J. Gong, et al., “Campylobacter Jejuni-Derived Cytolethal Distending Toxin Promotes Colorectal Cancer Metastasis,” Cell Host & Microbe 32, no. 12 (2024): 2080–2091.

[142] Q. Q. Liu, C. M. Li, L. N. Fu, et al., “Enterotoxigenic Bacteroides fragilis Induces the Stemness in Colorectal Cancer via Upregulating Histone Demethylase JMJD2B,” Gut Microbes 12, no. 1 (2020): 1788900.

[143] S. Guo, F. Chen, L. Li, et al., “Intracellular Fusobacterium nucleatum Infection Increases METTL3-Mediated m6A Methylation to Promote the Metastasis of Esophageal Squamous Cell Carcinoma,” Journal of Advanced Research 61 (2024): 165–178.

[144] Y. Zhang, L. Zhang, S. Zheng, et al., “Fusobacterium nucleatum Promotes Colorectal Cancer Cells Adhesion to Endothelial Cells and Facilitates Extravasation and Metastasis by Inducing ALPK1/NF-κB/ICAM1 Axis,” Gut Microbes 14, no. 1 (2022): 2038852.

[145] F. Gao, B. Yu, B. Rao, et al., “The Effect of the Intratumoral Microbiome on Tumor Occurrence, Progression, Prognosis and Treatment,” Frontiers in Immunology 13 (2022): 1051987.

[146] Y. Cao, Z. Wang, Y. Yan, et al., “Enterotoxigenic Bacteroides fragilis Promotes Intestinal Inflammation and Malignancy by Inhibiting Exosome-Packaged miR-149-3p,” Gastroenterology 161, no. 5 (2021): 1552–1566.e12.

[147] S. Guo, J. Chen, F. Chen, et al., “Exosomes Derived From Fusobacterium Nucleatum-Infected Colorectal Cancer Cells Facilitate Tumour Metastasis by Selectively Carrying miR-1246/92b-3p/27a-3p and CXCL16,” Gut 70 (2021): 1507–1519.

[148] R. Domenis, A. Cifù, D. Marinò, et al., “Toll-Like Receptor-4 Activation Boosts the Immunosuppressive Properties of Tumor Cells-Derived Exosomes,” Scientific Reports 9, no. 1 (2019): 8457.

[149] Y. Murota and C. Jobin, “Bacteria Break Barrier to Promote Metastasis,” Cancer Cell 39, no. 5 (2021): 598–600.

[150] A. Bertocchi, S. Carloni, P. S. Ravenda, et al., “Gut Vascular Barrier Impairment Leads to Intestinal Bacteria Dissemination and Colorectal Cancer Metastasis to Liver,” Cancer Cell 39, no. 5 (2021): 708–724.e11.

[151] M. Singhal and H. G. Augustin, “Beyond Angiogenesis: Exploiting Angiocrine Factors to Restrict Tumor Progression and Metastasis,” Cancer Research 80, no. 4 (2020): 659–662.

[152] A. Schirbel, S. Kessler, F. Rieder, et al., “Pro-Angiogenic Activity of TLRs and NLRs: A Novel Link Between Gut Microbiota and Intestinal Angiogenesis,” Gastroenterology 144, no. 3 (2013): 613–623.e9.

[153] X. Song, Y. An, and D. Chen, “Microbial Metabolite Deoxycholic Acid Promotes Vasculogenic Mimicry Formation in Intestinal Carcinogenesis,” Cancer Science 113, no. 2 (2022): 459–477.

[154] R. V. Purcell, J. Permain, and J. I. Keenan, “Enterotoxigenic Bacteroides fragilis Activates IL-8 Expression Through Stat3 in Colorectal Cancer Cells,” Gut Pathogens 14, no. 1 (2022): 16.

[155] J. Xu, Y. Tian, B. Zhao, et al., “Gut Microbiome Influences Efficacy of Endostatin Combined With PD-1 Blockade Against Colorectal Cancer,” Molecular Biomedicine 5, no. 1 (2024): 37.

[156] T. Zhang, Y. Li, E. Zhai, et al., “Intratumoral Fusobacterium nucleatum Recruits Tumor-Associated Neutrophils to Promote Gastric Cancer Progression and Immune Evasion,” Cancer Research 85, no. 10 (2025): 1819–1841.

[157] Y. Lu, L. Xu, W. Chen, et al., “Intrahepatic Microbial Heterogeneity in Multifocal Hepatocellular Carcinoma and Its Association With Host Genomic and Transcriptomic Alterations,” Cancer Discovery 15, no. 8 (2025): 1630–1648.

[158] B. M. Szczerba, F. Castro-Giner, M. Vetter, et al., “Neutrophils Escort Circulating Tumour Cells to Enable Cell Cycle Progression,” Nature 566, no. 7745 (2019): 553–557.

[159] C. Hu, L. Long, J. Lou, et al., “CTC-Neutrophil Interaction: A Key Driver and Therapeutic Target of Cancer Metastasis,” Biomedicine & Pharmacotherapy 180 (2024): 117474.

[160] P. Shen, P. Cheng, Y. Li, et al., “Unveiling the Covert Interaction Between Gut Microbiota and Neutrophils to Drive Colorectal Cancer Metastasis,” European Journal of Pharmacology 962 (2024): 176217.

[161] L. Yuan, L. Pan, Y. Wang, et al., “Characterization of the Landscape of the Intratumoral Microbiota Reveals That Streptococcus anginosus Increases the Risk of Gastric Cancer Initiation and Progression,” Cell Discovery 10, no. 1 (2024): 117.

[162] C. Gur, Y. Ibrahim, B. Isaacson, et al., “Binding of the Fap2 Protein of Fusobacterium nucleatum to Human Inhibitory Receptor TIGIT Protects Tumors From Immune Cell Attack,” Immunity 42, no. 2 (2015): 344–355.

[163] B. Udayasuryan, R. N. Ahmad, T. T. D. Nguyen, et al., “Fusobacterium nucleatum Induces Proliferation and Migration in Pancreatic Cancer Cells Through Host Autocrine and Paracrine Signaling,” Science Signaling 15, no. 756 (2022): eabn4948.

[164] R. Peng, S. Liu, W. You, et al., “Gastric Microbiome Alterations Are Associated With Decreased CD8+ Tissue-Resident Memory T Cells in the Tumor Microenvironment of Gastric Cancer,” Cancer Immunology Research 10, no. 10 (2022): 1224–1240.

[165] Z. C. Guo, S. L. Jing, X. Y. Jia, et al., “Porphyromonas gingivalis Promotes the Progression of Oral Squamous Cell Carcinoma by Stimulating the Release of Neutrophil Extracellular Traps in the Tumor Immune Microenvironment,” Inflammation Research: Official Journal of the European Histamine Research Society 73, no. 5 (2024): 693–705.

[166] H. Wu, X. Leng, Q. Liu, et al., “Intratumoral Microbiota Composition Regulates Chemoimmunotherapy Response in Esophageal Squamous Cell Carcinoma,” Cancer Research 83, no. 18 (2023): 3131–3144.

[167] G. Zhu, H. Su, C. H. Johnson, S. A. Khan, H. Kluger, and L. Lu, “Intratumour Microbiome Associated With the Infiltration of Cytotoxic CD8+ T Cells and Patient Survival in Cutaneous Melanoma,” European Journal of Cancer 151 (2021): 25–34.

[168] M. Xie, K. Yuan, Y. Zhang, et al., “Tumor-Resident Probiotic Clostridium Butyricum Improves aPD-1 Efficacy in Colorectal Cancer Models by Inhibiting IL-6-Mediated Immunosuppression,” Cancer Cell 43, no. 10 (2025): 1885–1901.e10.

[169] X. Wang, Y. Fang, W. Liang, et al., “Fusobacterium nucleatum Facilitates Anti-PD-1 Therapy in Microsatellite Stable Colorectal Cancer,” Cancer Cell 42, no. 10 (2024): 1729–1746, e8.

[170] J. Chen, Y. Gao, Y. Chen, et al., “Identification and Validation of Intratumoral Microbiome Associated With Sensitization to Immune Checkpoint Inhibitors,” Cell Reports Medicine 6, no. 9 (2025): 102306.

[171] S. S. Jiang, Y. L. Xie, X. Y. Xiao, et al., “Fusobacterium nucleatum-Derived Succinic Acid Induces Tumor Resistance to Immunotherapy in Colorectal Cancer,” Cell Host & Microbe 31, no. 5 (2023): 781–797.e9.

[172] J. Gu, X. Xu, X. Li, et al., “Tumor-Resident Microbiota Contributes to Colorectal Cancer Liver Metastasis by Lactylation and Immune Modulation,” Oncogene 43, no. 31 (2024): 2389–2404.

[173] M. J. Bender, A. C. McPherson, C. M. Phelps, et al., “Dietary Tryptophan Metabolite Released by Intratumoral Lactobacillus reuteri Facilitates Immune Checkpoint Inhibitor Treatment,” Cell 186, no. 9 (2023): 1846–1862, e26.

[174] J. Zhu, S. Qin, R. Gu, S. Ji, G. Wu, and K. Gu, “Amuc_1434 From Akkermansia Muciniphila Enhances CD8+ T Cell-Mediated Anti-Tumor Immunity by Suppressing PD-L1 in Colorectal Cancer,” FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology 39, no. 8 (2025): e70540.

[175] Z. Zhu, J. Cai, W. Hou, et al., “Microbiome and Spatially Resolved Metabolomics Analysis Reveal the Anticancer Role of Gut Akkermansia muciniphila by Crosstalk With Intratumoral Microbiota and Reprogramming Tumoral Metabolism in Mice,” Gut Microbes 15, no. 1 (2023): 2166700.

[176] J. Ma, L. Huang, D. Hu, S. Zeng, Y. Han, and H. Shen, “The Role of the Tumor Microbe Microenvironment in the Tumor Immune Microenvironment: Bystander, Activator, or Inhibitor?,” Journal of Experimental & Clinical Cancer Research: CR 40, no. 1 (2021): 327.

[177] N. Singh, A. Gurav, S. Sivaprakasam, et al., “Activation of Gpr109a, Receptor for Niacin and the Commensal Metabolite Butyrate, Suppresses Colonic Inflammation and Carcinogenesis,” Immunity 40, no. 1 (2014): 128–139.

[178] J. C. Drobner, B. J. Lichtbroun, E. A. Singer, and S. Ghodoussipour, “Examining the Role of Microbiota-Centered Interventions in Cancer Therapeutics: Applications for Urothelial Carcinoma,” Technology in Cancer Research & Treatment 22 (2023): 15330338231164196.

[179] X. Kang, C. Liu, Y. Ding, et al., “Roseburia intestinalis Generated Butyrate Boosts Anti-PD-1 Efficacy in Colorectal Cancer by Activating Cytotoxic CD8(+) T Cells,” Gut 72, no. 11 (2023): 2112–2122.

[180] C. Lu, Y. Liu, N. M. Ali, B. Zhang, and X. Cui, “The Role of Innate Immune Cells in the Tumor Microenvironment and Research Progress in Anti-tumor Therapy,” Frontiers in Immunology 13 (2022): 1039260.

[181] Q. Li, C. Ding, T. Meng, et al., “Butyrate Suppresses Motility of Colorectal Cancer Cells via Deactivating Akt/ERK Signaling in Histone Deacetylase Dependent Manner,” Journal of Pharmacological Sciences 135, no. 4 (2017): 148–155.

[182] L. M. Sipe, M. Chaib, A. K. Pingili, J. F. Pierre, and L. Makowski, “Microbiome, Bile Acids, and Obesity: How Microbially Modified Metabolites Shape Anti-Tumor Immunity,” Immunological Reviews 295, no. 1 (2020): 220–239.

[183] S. Xia, D. Jia, and L. Wang, “Microbiota: A Dawn for Cancer Metastasis Therapy,” Trends in Molecular Medicine (2025): 458–471.

[184] C. Li, X. Xing, M. Li, et al., “Bile Acids Produced by Gut Microbiota Activate TGR5 to Promote Colorectal Liver Metastasis Progression by Inducing MDSCs Infiltration in Liver,” International Immunopharmacology 158 (2025): 114829.

[185] T. Wang, J. N. R. Gnanaprakasam, X. Chen, et al., “Inosine Is an Alternative Carbon Source for CD8(+)-T-Cell Function Under Glucose Restriction,” Nature Metabolism 2, no. 7 (2020): 635–647.

[186] L. F. Mager, R. Burkhard, N. Pett, et al., “Microbiome-Derived Inosine Modulates Response to Checkpoint Inhibitor Immunotherapy,” Science 369, no. 6510 (2020): 1481–1489.

[187] W. Li, W. Shangguan, W. Huang, et al., “Gut Parabacteroides distasonis-Derived Indole-3-Acetic Acid Promotes Phospholipid Remodeling and Enhances Ferroptosis Sensitivity via the AhR-FASN Axis in Bladder Cancer,” Advanced Science 12, no. 34 (2025): e04688.

[188] K. Hezaveh, R. S. Shinde, A. Klötgen, et al., “Tryptophan-Derived Microbial Metabolites Activate the Aryl Hydrocarbon Receptor in Tumor-Associated Macrophages to Suppress Anti-Tumor Immunity,” Immunity 55, no. 2 (2022): 324–340, e8.

[189] Q. Zhang, Q. Zhao, T. Li, et al., “Lactobacillus plantarum-Derived Indole-3-lactic Acid Ameliorates Colorectal Tumorigenesis via Epigenetic Regulation of CD8(+) T Cell Immunity,” Cell Metabolism 35, no. 6 (2023): 943–960.e9.

[190] L. E. Colbert, M. B. El Alam, R. Wang, et al., “Tumor-Resident Lactobacillus iners Confer Chemoradiation Resistance Through Lactate-Induced Metabolic Rewiring,” Cancer Cell 41, no. 11 (2023): 1945–1962.e11.

[191] H. Yu, Y. Du, Y. He, et al., “Lactate Production by Tumor-Resident Staphylococcus Promotes Metastatic Colonization in Lung Adenocarcinoma,” Cell Host & Microbe 33, no. 7 (2025): 1089–1105, e7.

[192] K. Vinasco, H. M. Mitchell, N. O. Kaakoush, and N. Castaño-Rodríguez, “Microbial Carcinogenesis: Lactic Acid Bacteria in Gastric Cancer,” Biochimica et Biophysica Acta Reviews on Cancer 1872, no. 2 (2019): 188309.

[193] X. Pan, F. Ye, P. Ning, et al., “Structures of G-Protein Coupled Receptor HCAR1 in Complex With Gi1 Protein Reveal the Mechanistic Basis for Ligand Recognition and Agonist Selectivity,” PLoS Biology 23, no. 4 (2025): e3003126.

[194] Y. S. Lee, T. Y. Kim, Y. Kim, et al., “Microbiota-Derived Lactate Accelerates Intestinal Stem-Cell-Mediated Epithelial Development,” Cell Host & Microbe 24, no. 6 (2018): 833–846.

[195] H. Wang, X. Rong, G. Zhao, et al., “The Microbial Metabolite Trimethylamine N-oxide Promotes Antitumor Immunity in Triple-Negative Breast Cancer,” Cell Metabolism 34, no. 4 (2022): 581–594, e8.

[196] K. C. Lam, R. E. Araya, A. Huang, et al., “Microbiota Triggers STING-type I IFN-Dependent Monocyte Reprogramming of the Tumor Microenvironment,” Cell 184, no. 21 (2021): 5338–5356, e21.

[197] G. Dalmasso, A. Cougnoux, T. Faïs, et al., “Colibactin-Producing Escherichia coli Enhance Resistance to Chemotherapeutic Drugs by Promoting Epithelial to Mesenchymal Transition and Cancer Stem Cell Emergence,” Gut Microbes 16, no. 1 (2024): 2310215.

[198] W. Ma, L. Zhang, W. Chen, et al., “Microbiota Enterotoxigenic Bacteroides fragilis-Secreted BFT-1 Promotes Breast Cancer Cell Stemness and Chemoresistance Through Its Functional Receptor NOD1,” Protein & Cell 15, no. 6 (2024): 419–440.

[199] S. Wu, P. J. Morin, D. Maouyo, and C. L. Sears, “Bacteroides fragilis Enterotoxin Induces c-Myc Expression and Cellular Proliferation,” Gastroenterology 124, no. 2 (2003): 392–400.

[200] Q. Tan, X. Ma, B. Yang, et al., “Periodontitis Pathogen Porphyromonas gingivalis Promotes Pancreatic Tumorigenesis via Neutrophil Elastase From Tumor-Associated Neutrophils,” Gut Microbes 14, no. 1 (2022): 2073785.

[201] J. Ren, X. Han, H. Lohner, et al., “P. gingivalis Infection Upregulates PD-L1 Expression on Dendritic Cells, Suppresses CD8+ T-Cell Responses, and Aggravates Oral Cancer,” Cancer Immunology Research 11, no. 3 (2023): 290–305.

[202] N. H. Ha, B. H. Woo, D. J. Kim, et al., “Prolonged and Repetitive Exposure to Porphyromonas gingivalis Increases Aggressiveness of Oral Cancer Cells by Promoting Acquisition of Cancer Stem Cell Properties,” Tumour Biology: The Journal of the International Society for Oncodevelopmental Biology and Medicine 36, no. 12 (2015): 9947–9960.

[203] A. Javaheri, T. Kruse, K. Moonens, et al., “Helicobacter pylori Adhesin HopQ Engages in a Virulence-Enhancing Interaction With Human CEACAMs,” Nature Microbiology 2 (2016): 16189.

[204] C. Gur, N. Maalouf, M. Gerhard, et al., “The Helicobacter pylori HopQ Outermembrane Protein Inhibits Immune Cell Activities,” Oncoimmunology 8, no. 4 (2019): e1553487.

[205] R. Luo, Y. Yao, Z. Chen, and X. Sun, “An Examination of the LPS-TLR4 Immune Response Through the Analysis of Molecular Structures and Protein-Protein Interactions,” Cell Communication and Signaling: CCS 23, no. 1 (2025): 142.

[206] C. L. Dixon, A. Wu, and G. D. Fairn, “Multifaceted Roles and Regulation of Nucleotide-Binding Oligomerization Domain Containing Proteins,” Frontiers in Immunology 14 (2023): 1242659.

[207] J. Karta, M. Meyers, F. Rodriguez, et al., “Fusobacterium nucleatum Interacts With Cancer-Associated Fibroblasts to Promote Colorectal Cancer,” EMBO Journal 44, no. 19 (2025): 5375–5393.

[208] X. He, J. Guo, Y. Bai, H. Sun, and J. Yang, “Salmonella-Based Therapeutic Strategies: Improving Tumor Microenvironment and Bringing New Hope for Cancer Immunotherapy,” Medical Oncology 42, no. 1 (2024): 27.

[209] H. Wang, B. Lin, Z. Wang, et al., “Fusobacterium nucleatum Increases CTGF Expression Through TLR2-YAP Signaling Axis in Cancer-Associated Fibroblasts, Thereby Promoting Colorectal Cancer Progression,” Cancer Cell International 25, no. 1 (2025): 381.

[210] W. Cheng, Y. Liao, Y. Xie, et al., “Helicobacter pylori-Induced Fibroblast-Derived Serpin E1 Promotes Gastric Cancer Growth and Peritoneal Dissemination Through p38 MAPK/VEGFA-mediated Angiogenesis,” Cancer Cell International 23, no. 1 (2023): 326.

[211] J. Li, X. Li, Z. Zhang, et al., “Helicobacter pylori Promotes Gastric Fibroblast Proliferation and Migration by Expulsing Exosomal miR-124-3p,” Microbes and Infection 26, no. 1–2 (2024): 105236.

[212] X. Long, C. C. Wong, L. Tong, et al., “Peptostreptococcus Anaerobius Promotes Colorectal Carcinogenesis and Modulates Tumour Immunity,” Nature Microbiology 4, no. 12 (2019): 2319–2330.

[213] S. Ruggiero, R. Cosgarea, J. Potempa, B. Potempa, S. Eick, and M. Chiquet, “Cleavage of Extracellular Matrix in Periodontitis: Gingipains Differentially Affect Cell Adhesion Activities of Fibronectin and Tenascin-C,” Biochimica et Biophysica Acta 1832, no. 4 (2013): 517–526.

[214] X. Zhou, L. Chen, W. Lin, W. Zheng, H. Zhang, and F. Zhou, “Diagnostic and Prognostic Potential of the Intra-Tumoral Microbiota Profile in HPV-Independent Endocervical Adenocarcinoma,” Frontiers in Cellular and Infection Microbiology 14 (2024): 1440017.

[215] W. Wang, C. Qian, T. Wang, et al., “A Combination of Faecal and Intratumour Microbial Community Profiling Reveals Novel Diagnostic and Prognostic Biomarkers for Pancreatic Tumours,” Clinical and Translational Medicine 14, no. 6 (2024): e1726.

[216] X. Fan, A. V. Alekseyenko, J. Wu, et al., “Human Oral Microbiome and Prospective Risk for Pancreatic Cancer: A Population-Based Nested Case-Control Study,” Gut 67, no. 1 (2018): 120–127.

[217] L. Sun, X. Ke, A. Guan, et al., “Intratumoural Microbiome Can Predict the Prognosis of Hepatocellular Carcinoma After Surgery,” Clinical and Translational Medicine 13, no. 7 (2023): e1331.

[218] M. Hilmi, M. Kamal, S. Vacher, et al., “Intratumoral Microbiome Is Driven by Metastatic Site and Associated With Immune Histopathological Parameters: An Ancillary Study of the SHIVA Clinical Trial,” European Journal of Cancer 183 (2023): 152–161.

[219] H. Qiao, X. R. Tan, H. Li, et al., “Association of Intratumoral Microbiota with Prognosis in Patients With Nasopharyngeal Carcinoma From 2 Hospitals in China,” JAMA Oncology 8, no. 9 (2022): 1301–1309.

[220] X.-R. Tan, H. Qiao, Y.-Q. Li, et al., “Tissue-Resident Microbiota Signature in Nasopharyngeal Carcinoma,” Microbiome 13, no. 1 (2025): 125.

[221] D. Qu, Y. Wang, Q. Xia, J. Chang, X. Jiang, and H. Zhang, “Intratumoral Microbiome of Human Primary Liver Cancer,” Hepatology Communications 6, no. 7 (2022): 1741–1752.

[222] S. Y. Kwon, H. Thi-Thu Ngo, J. Son, Y. Hong, and J. J. Min, “Exploiting Bacteria for Cancer Immunotherapy,” Nature Reviews Clinical Oncology 21, no. 8 (2024): 569–589.

[223] Y. Goto, S. Iwata, M. Miyahara, and E. Miyako, “Discovery of Intratumoral Oncolytic Bacteria Toward Targeted Anticancer Theranostics,” Advanced Science 10, no. 20 (2023): e2301679.

[224] S. Yan, T. Liu, H. Zhao, et al., “Colorectal Cancer-Specific Microbiome in Peripheral Circulation and Cancer Tissues,” Frontiers in Microbiology 15 (2024): 1422536.

[225] H. J. An, M. A. Partha, H. Lee, et al., “Tumor-Associated Microbiome Features of Metastatic Colorectal Cancer and Clinical Implications,” Frontiers in Oncology 13 (2023): 1310054.

[226] G. Wang, H. Wang, X. Ji, et al., “Intratumoral Microbiome Is Associated With Gastric Cancer Prognosis and Therapy Efficacy,” Gut Microbes 16, no. 1 (2024): 2369336.

[227] K. Yamamura, D. Izumi, R. Kandimalla, et al., “Intratumoral Fusobacterium Nucleatum Levels Predict Therapeutic Response to Neoadjuvant Chemotherapy in Esophageal Squamous Cell Carcinoma,” Clinical Cancer Research: An Official Journal of the American Association for Cancer Research 25, no. 20 (2019): 6170–6179.

[228] S. T. Huang, J. Chen, and L. Y. Lian, “Intratumoral Levels and Prognostic Significance of Fusobacterium nucleatum in Cervical Carcinoma,” Aging 12, no. 22 (2020): 23337–23350.

[229] A. Pribluda, C. C. de la Cruz, and E. L. Jackson, “Intratumoral Heterogeneity: From Diversity Comes Resistance,” Clinical Cancer Research: An Official Journal of the American Association for Cancer Research 21, no. 13 (2015): 2916–2923.

[230] K. Khalaf, D. Hana, J. T. Chou, C. Singh, A. Mackiewicz, and M. Kaczmarek, “Aspects of the Tumor Microenvironment Involved in Immune Resistance and Drug Resistance,” Frontiers in Immunology 12 (2021): 656364.

[231] A. Sevcikova, N. Izoldova, V. Stevurkova, et al., “The Impact of the Microbiome on Resistance to Cancer Treatment With Chemotherapeutic Agents and Immunotherapy,” International Journal of Molecular Sciences 23, no. 1 (2022): e83744.

[232] C. Xuan, J. M. Shamonki, A. Chung, et al., “Microbial Dysbiosis Is Associated With human Breast Cancer,” PLoS ONE 9, no. 1 (2014): e83744.

[233] D. S. Michaud, J. Izard, C. S. Wilhelm-Benartzi, et al., “Plasma Antibodies to Oral Bacteria and Risk of Pancreatic Cancer in a Large European Prospective Cohort Study,” Gut 62, no. 12 (2013): 1764–1770.

[234] C. Panebianco, A. Andriulli, and V. Pazienza, “Pharmacomicrobiomics: Exploiting the Drug-microbiota Interactions in Anticancer Therapies,” Microbiome 6, no. 1 (2018): 92.

[235] P. Lehouritis, J. Cummins, M. Stanton, et al., “Local Bacteria Affect the Efficacy of Chemotherapeutic Drugs,” Scientific Reports 5 (2015): 14554.

[236] N. Wang, L. Zhang, X. X. Leng, et al., “Fusobacterium nucleatum Induces Chemoresistance in Colorectal Cancer by Inhibiting Pyroptosis via the Hippo Pathway,” Gut Microbes 16, no. 1 (2024): 2333790.

[237] B. Li, Z. Wei, Z. Wang, et al., “Fusobacterium nucleatum Induces Oxaliplatin Resistance by Inhibiting Ferroptosis Through E-Cadherin/β-Catenin/GPX4 Axis in Colorectal Cancer,” Free Radical Biology & Medicine 220 (2024): 125–138.

[238] R. Daillère, M. Vétizou, N. Waldschmitt, et al., “Enterococcus Hirae and Barnesiella Intestinihominis Facilitate Cyclophosphamide-Induced Therapeutic Immunomodulatory Effects,” Immunity 45, no. 4 (2016): 931–943.

[239] S. Viaud, F. Saccheri, G. Mignot, et al., “The Intestinal Microbiota Modulates the Anticancer Immune Effects of Cyclophosphamide,” Science 342, no. 6161 (2013): 971–976.

[240] J. Liu, C. Liu, and J. Yue, “Radiotherapy and the Gut Microbiome: Facts and Fiction,” Radiation Oncology 16, no. 1 (2021): 9.

[241] G. Serna, F. Ruiz-Pace, J. Hernando, et al., “Fusobacterium nucleatum Persistence and Risk of Recurrence After Preoperative Treatment in Locally Advanced Rectal Cancer,” Annals of Oncology: Official Journal of the European Society for Medical Oncology 31, no. 10 (2020): 1366–1375.

[242] K. Yang, Y. Hou, Y. Zhang, et al., “Suppression of Local Type I Interferon by Gut Microbiota-Derived Butyrate Impairs Antitumor Effects of Ionizing Radiation,” Journal of Experimental Medicine 218, no. 3 (2021): e20201915.

[243] X. Huang, C. Chen, W. Xie, et al., “Metagenomic Analysis of Intratumoral Microbiome Linking to Response to Neoadjuvant Chemoradiotherapy in Rectal Cancer,” International Journal of Radiation and Oncology in Biology and Physics 117, no. 5 (2023): 1255–1269.

[244] J. Noguti, A. A. Chan, B. Bandera, et al., “Both the Intratumoral Immune and Microbial Microenvironment Are Linked to Recurrence in Human Colon Cancer: Results From a Prospective, Multicenter Nodal Ultrastaging Trial,” Oncotarget 9, no. 34 (2018): 23564–23576.

[245] C. Neuzillet, M. Marchais, S. Vacher, et al., “Prognostic Value of Intratumoral Fusobacterium nucleatum and Association With Immune-Related Gene Expression in Oral Squamous Cell Carcinoma Patients,” Scientific Reports 11, no. 1 (2021): 7870.

[246] S. L. Shiao, K. M. Kershaw, J. J. Limon, et al., “Commensal Bacteria and Fungi Differentially Regulate Tumor Responses to Radiation Therapy,” Cancer Cell 39, no. 9 (2021): 1202–1213, e6.

[247] H. Guo, W. C. Chou, Y. Lai, et al., “Multi-Omics Analyses of Radiation Survivors Identify Radioprotective Microbes and Metabolites,” Science 370, no. 6516 (2020): eaay9097.

[248] A. D. Waldman, J. M. Fritz, and M. J. Lenardo, “A Guide to Cancer Immunotherapy: From T Cell Basic Science to Clinical Practice,” Nature Reviews Immunology 20, no. 11 (2020): 651–668.

[249] M. Vétizou, J. M. Pitt, R. Daillère, et al., “Anticancer Immunotherapy by CTLA-4 Blockade Relies on the Gut Microbiota,” Science 350, no. 6264 (2015): 1079–1084.

[250] A. Sivan, L. Corrales, N. Hubert, et al., “Commensal Bifidobacterium Promotes Antitumor Immunity and Facilitates Anti-PD-L1 Efficacy,” Science 350, no. 6264 (2015): 1084–1089.

[251] B. Routy, E. Le Chatelier, and L. Derosa, “Gut Microbiome Influences Efficacy of PD-1-Based Immunotherapy Against Epithelial Tumors,” Science 359, no. 6371 (2018): 91–97.

[252] D. Davar, A. K. Dzutsev, J. A. McCulloch, et al., “Fecal Microbiota Transplant Overcomes Resistance to Anti-PD-1 Therapy in Melanoma Patients,” Science 371, no. 6529 (2021): 595–602.

[253] E. N. Baruch, I. Youngster, G. Ben-Betzalel, et al., “Fecal Microbiota Transplant Promotes Response in Immunotherapy-Refractory Melanoma Patients,” Science 371, no. 6529 (2021): 602–609.

[254] N. Dizman, L. Meza, P. Bergerot, et al., “Nivolumab Plus Ipilimumab With or Without Live Bacterial Supplementation in Metastatic Renal Cell Carcinoma: A Randomized Phase 1 Trial,” Nature Medicine 28, no. 4 (2022): 704–712.

[255] Z. Liu, X. Zhang, H. Zhang, et al., “Multi-Omics Analysis Reveals Intratumor Microbes as Immunomodulators in Colorectal Cancer,” Microbiology Spectrum 11, no. 2 (2023): e0503822.

[256] Y. Li, S. Xing, F. Chen, et al., “Intracellular Fusobacterium nucleatum Infection Attenuates Antitumor Immunity in Esophageal Squamous Cell Carcinoma,” Nature Communications 14, no. 1 (2023): 5788.

[257] F. Chen, J. Yang, Y. Guo, D. Su, Y. Sheng, and Y. Wu, “Integrating Bulk and Single-Cell RNA Sequencing Data Reveals the Relationship Between Intratumor Microbiome Signature and Host Metabolic Heterogeneity in Breast Cancer,” Frontiers in Immunology 14 (2023): 1140995.

[258] A. Panda, J. M. Mehnert, K. M. Hirshfield, et al., “Immune Activation and Benefit from Avelumab in EBV-Positive Gastric Cancer,” Journal of the National Cancer Institute 110, no. 3 (2018): 316–320.

[259] Y. Huang, N. Zhu, X. Zheng, et al., “Intratumor Microbiome Analysis Identifies Positive Association Between Megasphaera and Survival of Chinese Patients With Pancreatic Ductal Adenocarcinomas,” Frontiers in Immunology 13 (2022): 785422.

[260] S. Chu, Z. Cheng, Z. Yin, et al., “Airway Fusobacterium Is Associated With Poor Response to Immunotherapy in Lung Cancer,” OncoTargets and Therapy 15 (2022): 201–213.

[261] L. Derosa, B. Routy, A. M. Thomas, et al., “Intestinal Akkermansia Muciniphila Predicts Clinical Response to PD-1 Blockade in Patients With Advanced Non-Small-Cell Lung Cancer,” Nature Medicine 28, no. 2 (2022): 315–324.

[262] J. S. Park, F. S. Gazzaniga, M. Wu, et al., “Targeting PD-L2-RGMb Overcomes Microbiome-related Immunotherapy Resistance,” Nature 617, no. 7960 (2023): 377–385.

[263] L. Chen, J. Shen, Z. Kang, et al., “Fusobacterium nucleatum-Mimicking Nanovehicles to Overcome Chemoresistance for Breast Cancer Treatment by Eliminating Tumor-Colonizing Bacteria,” Chemistry 10, no. 6 (2024): 1783–1803.

[264] S. Geng, P. Guo, X. Li, et al., “Biomimetic Nanovehicle-Enabled Targeted Depletion of Intratumoral Fusobacterium nucleatum Synergizes With PD-L1 Blockade Against Breast Cancer,” ACS Nano 18, no. 12 (2024): 8971–8987.

[265] J. R. Whittle, J. D. Lickliter, H. K. Gan, et al., “First in Human Nanotechnology Doxorubicin Delivery System to Target Epidermal Growth Factor Receptors in Recurrent Glioblastoma,” Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia 22, no. 12 (2015): 1889–1894.

[266] T. M. Savage, R. L. Vincent, S. S. Rae, et al., “Chemokines Expressed by Engineered Bacteria Recruit and Orchestrate Antitumor Immunity,” Science Advances 9, no. 10 (2023): eadc9436.

[267] Y. Qiao, M. Luo, Y. Wang, et al., “Development of a Bacteria-Nanosapper for the Active Delivery of ZIF-8 Particles Containing Therapeutic Genes for Cancer Immune Therapy,” Acta Pharmaceutica Sinica B 14, no. 12 (2024): 5418–5434.

[268] Z. Chang, X. Guo, X. Li, et al., “Bacterial Immunotherapy Leveraging IL-10R Hysteresis for Both Phagocytosis Evasion and Tumor Immunity Revitalization,” Cell 188, no. 7 (2025): 1842–1857, e20.

[269] J. J. Luke, S. A. Piha-Paul, T. Medina, et al., “Phase I Study of SYNB1891, an Engineered E. coli Nissle Strain Expressing STING Agonist, With and Without Atezolizumab in Advanced Malignancies,” Clinical Cancer Research: An Official Journal of the American Association for Cancer Research 29, no. 13 (2023): 2435–2444.

[270] J. F. Toso, V. J. Gill, P. Hwu, et al., “Phase I Study of the Intravenous Administration of Attenuated Salmonella Typhimurium to Patients With Metastatic Melanoma,” Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology 20, no. 1 (2002): 142–152.

[271] L. Guo, J. Ding, and W. Zhou, “Converting Bacteria Into Autologous Tumor Vaccine via Surface Biomineralization of Calcium Carbonate for Enhanced Immunotherapy,” Acta Pharmaceutica Sinica B 13, no. 12 (2023): 5074–5090.

[272] Z. Kang, L. Chen, P. Li, et al., “A Polyvalent Vaccine for Selectively Killing Tumor-Associated Bacteria to Prevent Cancer Metastasis,” Science Advances 11, no. 11 (2025): eadt0341.

[273] F. H. Schmitz-Winnenthal, N. Hohmann, A. G. Niethammer, et al., “Anti-Angiogenic Activity of VXM01, an Oral T-Cell Vaccine Against VEGF Receptor 2, in Patients With Advanced Pancreatic Cancer: A Randomized, Placebo-Controlled, Phase 1 Trial,” Oncoimmunology 4, no. 4 (2015): e1001217.

[274] D. T. Le, A. Wang-Gillam, V. Picozzi, et al., “Safety and Survival With GVAX Pancreas Prime and Listeria Monocytogenes-Expressing Mesothelin (CRS-207) Boost Vaccines for Metastatic Pancreatic Cancer,” Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology 33, no. 12 (2015): 1325–1333.

[275] T. Tsujikawa, T. Crocenzi, J. N. Durham, et al., “Evaluation of Cyclophosphamide/GVAX Pancreas Followed by Listeria-Mesothelin (CRS-207) With or Without Nivolumab in Patients With Pancreatic Cancer,” Clinical Cancer Research: An Official Journal of the American Association for Cancer Research 26, no. 14 (2020): 3578–3588.

[276] F. Janku, H. H. Zhang, A. Pezeshki, et al., “Intratumoral Injection of Clostridium Novyi-NT Spores in Patients With Treatment-Refractory Advanced Solid Tumors,” Clinical Cancer Research: An Official Journal of the American Association for Cancer Research 27, no. 1 (2021): 96–106.

[277] S. Chintalapati, S. Iwata, M. Miyahara, and E. Miyako, “Tumor-Isolated Cutibacterium acnes as an Effective Tumor Suppressive Living Drug,” Biomedicine & Pharmacotherapy 170 (2024): 116041.

[278] M. Wang, B. Rousseau, K. Qiu, et al., “Killing Tumor-Associated Bacteria With a Liposomal Antibiotic Generates Neoantigens That Induce Anti-Tumor Immune Responses,” Nature Biotechnology 42, no. 8 (2024): 1263–1274.

[279] D. W. Zheng, X. Dong, P. Pan, et al., “Phage-Guided Modulation of the Gut Microbiota of Mouse Models of Colorectal Cancer Augments Their Responses to Chemotherapy,” Nature Biomedical Engineering 3, no. 9 (2019): 717–728.

[280] H. Guo, “Interactions Between the Tumor Microbiota and Breast Cancer,” Frontiers in Cellular and Infection Microbiology 14 (2024): 1499203.

[281] S. Matsumoto, T. Hara, M. Nagaoka, et al., “A Component of Polysaccharide Peptidoglycan Complex on Lactobacillus Induced an Improvement of Murine Model of Inflammatory Bowel Disease and Colitis-Associated Cancer,” Immunology 128 (2009): e170–e180.

[282] X. Li, H. Wang, X. Du, et al., “Lactobacilli Inhibit Cervical Cancer Cell Migration in Vitro and Reduce Tumor Burden in Vivo Through Upregulation of E-Cadherin,” Oncology Reports 38, no. 3 (2017): 1561–1568.

[283] H. Ebrahimi, N. Dizman, L. Meza, et al., “Cabozantinib and Nivolumab With or Without Live Bacterial Supplementation in Metastatic Renal Cell Carcinoma: A Randomized Phase 1 Trial,” Nature Medicine 30, no. 9 (2024): 2576–2585.

[284] R. L. Vincent, C. R. Gurbatri, F. Li, et al., “Probiotic-Guided CAR-T Cells for Solid Tumor Targeting,” Science 382, no. 6667 (2023): 211–218.

[285] N. Aggarwal, A. M. E. Breedon, C. M. Davis, I. Y. Hwang, and M. W. Chang, “Engineering Probiotics for Therapeutic Applications: Recent Examples and Translational Outlook,” Current Opinion in Biotechnology 65 (2020): 171–179.

[286] W. Li, X. Ma, and X. Zhao, “Intratumoral Microorganisms and Artificial Antitumor Bacteria,” Fundamental Research 5, no. 5 (2025): 2045–2048.

[287] Z. Y. Han, Z. J. Fu, Y. Z. Wang, et al., “Probiotics Functionalized With a Gallium-Polyphenol Network Modulate the Intratumor Microbiota and Promote Anti-Tumor Immune Responses in Pancreatic Cancer,” Nature Communications 15, no. 1 (2024): 7096.

[288] R. J. Knippel, J. L. Drewes, and C. L. Sears, “The Cancer Microbiome: Recent Highlights and Knowledge Gaps,” Cancer Discovery 11, no. 10 (2021): 2378–2395.

[289] M. Kabwe, S. Dashper, G. Bachrach, and J. Tucci, “Bacteriophage Manipulation of the Microbiome Associated With Tumour Microenvironments—Can This Improve Cancer Therapeutic Response?,” FEMS Microbiology Reviews 45, no. 5 (2021): fuab017.

[290] J. Li, C. Zhang, X. Huang, et al., “Candida albicans Synergizes With Fusobacteriumnucleatum in Colorectal Cancer Progression via the Flo9-RadD Interaction,” Cancer Cell (2026): 1063–1079.e8.

[291] B. Aykut, S. Pushalkar, R. Chen, et al., “The Fungal Mycobiome Promotes Pancreatic Oncogenesis via Activation of MBL,” Nature 574, no. 7777 (2019): 264–267.

[292] N. N. Liu, C. X. Yi, L. Q. Wei, et al., “The Intratumor Mycobiome Promotes Lung Cancer Progression via Myeloid-Derived Suppressor Cells,” Cancer Cell 42, no. 2 (2024): 318–322.

[293] J. J. Roetman, M. K. I. Apostolova, and M. Philip, “Viral and Cellular Oncogenes Promote Immune Evasion,” Oncogene 41, no. 7 (2022): 921–929.

[294] S. Nakao, Y. Arai, M. Tasaki, et al., “Intratumoral Expression of IL-7 and IL-12 Using an Oncolytic Virus Increases Systemic Sensitivity to Immune Checkpoint Blockade,” Science Translational Medicine 12, no. 526 (2020): eaax7992.

[295] T. T. Nguyen, D. H. Shin, S. Sohoni, et al., “Reshaping the Tumor Microenvironment With Oncolytic Viruses, Positive Regulation of the Immune Synapse, and Blockade of the Immunosuppressive Oncometabolic Circuitry,” Journal for ImmunoTherapy of Cancer 10, no. 7 (2022): e004935.

Rights & permissions

2026 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.