Intravital microscopy contribution to cancer: From preclinical to human studies

Diogo Moniz-Garcia , Wan-Hsin Lin , Loizos Michaelides , Anthony Quagliano , Emmanuel Gabriel , Alfredo Quinones-Hinojosa

Clinical and Translational Discovery ›› 2025, Vol. 5 ›› Issue (5) : e70051

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Clinical and Translational Discovery ›› 2025, Vol. 5 ›› Issue (5) :e70051 DOI: 10.1002/ctd2.70051
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Intravital microscopy contribution to cancer: From preclinical to human studies

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Abstract

Intravital microscopy enables dynamic and real-time visualisation of microscopic structures in living tissues without the need for fixation, with real-life applicability being illustrated by several first-in-human studies in different cancers. Its use in preclinical models has yielded important observations of the microvasculature of both healthy and diseased tissues. It has further enabled the observation of the interactions between important components of the tissue microenvironment such as immune cells and neighbouring microvessels. Important recent technological advances, however, have enabled the translation of this technology to human use. Here, we review the main advances in intravital microscopy and some of the most recent uses in different human disease settings.

Keywords

blood‒brain barrier / brain / cancer / microscopy / technology / vasculature

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Diogo Moniz-Garcia, Wan-Hsin Lin, Loizos Michaelides, Anthony Quagliano, Emmanuel Gabriel, Alfredo Quinones-Hinojosa. Intravital microscopy contribution to cancer: From preclinical to human studies. Clinical and Translational Discovery, 2025, 5(5): e70051 DOI:10.1002/ctd2.70051

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References

[1]

Lin WH, Cooper LM, Anastasiadis PZ. Cadherins and catenins in cancer: connecting cancer pathways and tumor microenvironment. Front Cell Dev Biol. 2023; 11:1137013.

[2]

Lin Q, Choyke PL, Sato N. Visualizing vasculature and its response to therapy in the tumor microenvironment. Theranostics. 2023; 13(15): 5223-5246.

[3]

Jain RK, Munn LL, Fukumura D. Dissecting tumour pathophysiology using intravital microscopy. Nat Rev Cancer. 2002; 2(4): 266-276.

[4]

Entenberg D, Oktay MH, Condeelis JS. Intravital imaging to study cancer progression and metastasis. Nat Rev Cancer. 2023; 23(1): 25-42.

[5]

Gabriel EM, Fisher DT, Evans S, Takabe K, Skitzki JJ. Intravital microscopy in the study of the tumor microenvironment: from bench to human application. Oncotarget. 2018; 9(28): 20165-20178.

[6]

Miller MA, Weissleder R. Imaging of anticancer drug action in single cells. Nat Rev Cancer. 2017; 17(7): 399-414.

[7]

van Rheenen J, Scheele C. Intravital microscopy to illuminate cell state plasticity during metastasis. Curr Opin Cell Biol. 2021; 72: 28-35.

[8]

Pittet MJ, Weissleder R. Intravital imaging. Cell. 2011; 147(5): 983-991.

[9]

Coste A, Oktay MH, Condeelis JS, Entenberg D. Intravital imaging techniques for biomedical and clinical research. Cytometry A. 2020; 97(5): 448-457.

[10]

Scheele C, Herrmann D, Yamashita E, et al. Multiphoton intravital microscopy of rodents. Nat Rev Methods Primers. 2022; 2: 89.

[11]

Fisher DT, Muhitch JB, Kim M, et al. Intraoperative intravital microscopy permits the study of human tumour vessels. Nat Commun. 2016; 7:10684.

[12]

Gabriel EM, Sukniam K, Popp K, Bagaria SP. Human intravital microscopy in the study of sarcomas: an early trial of feasibility. Front Oncol. 2023; 13:1151255.

[13]

Garcia DM, Gabriel E, Quinones-Hinojosa A. Direct real-time intra-operative imaging of human brain tumour vessels using intravital microscopy. Clin Transl Med. 2024; 14(12):e70084.

[14]

Gabriel EM, Sukniam K, Popp K, et al. Human tumour vessel heterogeneity in ovarian cancer and its association with response to neoadjuvant chemotherapy. Clin Transl Med. 2024; 14(4):e1633.

[15]

Quester R, Schroder R. The shrinkage of the human brain stem during formalin fixation and embedding in paraffin. J Neurosci Methods. 1997; 75(1): 81-89.

[16]

Vincent A, Herman J, Schulick R, Hruban RH, Goggins M. Pancreatic cancer. Lancet. 2011; 378(9791): 607-620.

[17]

Beatty GL, Werba G, Lyssiotis CA, Simeone DM. The biological underpinnings of therapeutic resistance in pancreatic cancer. Genes Dev. 2021; 35(13-14): 940-962.

[18]

Samuel T, Rapic S, O'Brien C, Edson M, Zhong Y, DaCosta RS. Quantitative intravital imaging for real-time monitoring of pancreatic tumor cell hypoxia and stroma in an orthotopic mouse model. Sci Adv. 2023; 9(23):eade8672.

[19]

Zijlstra A, Lewis J, Degryse B, Stuhlmann H, Quigley JP. The inhibition of tumor cell intravasation and subsequent metastasis via regulation of in vivo tumor cell motility by the tetraspanin CD151. Cancer Cell. 2008; 13(3): 221-234.

[20]

Harney AS, Arwert EN, Entenberg D, et al. Real-time imaging reveals local, transient vascular permeability, and tumor cell intravasation stimulated by TIE2hi macrophage-derived VEGFA. Cancer Discov. 2015; 5(9): 932-943.

[21]

Rohan TE, Xue X, Lin HM, et al. Tumor microenvironment of metastasis and risk of distant metastasis of breast cancer. J Natl Cancer Inst. 2014; 106(8):dju136.

[22]

Sharma VP, Tang B, Wang Y, et al. Live tumor imaging shows macrophage induction and TMEM-mediated enrichment of cancer stem cells during metastatic dissemination. Nat Commun. 2021; 12(1): 7300.

[23]

Fumagalli A, Oost KC, Kester L, et al. Plasticity of Lgr5-negative cancer cells drives metastasis in colorectal cancer. Cell Stem Cell. 2020; 26(4): 569-578.e7.

[24]

Headley MB, Bins A, Nip A, et al. Visualization of immediate immune responses to pioneer metastatic cells in the lung. Nature. 2016; 531(7595): 513-517.

[25]

Nakasone ES, Askautrud HA, Kees T, et al. Imaging tumor-stroma interactions during chemotherapy reveals contributions of the microenvironment to resistance. Cancer Cell. 2012; 21(4): 488-503.

[26]

Miller MA, Chandra R, Cuccarese MF, et al. Radiation therapy primes tumors for nanotherapeutic delivery via macrophage-mediated vascular bursts. Sci Transl Med. 2017; 9(392):eaal0225.

[27]

Jain RK. Antiangiogenesis strategies revisited: from starving tumors to alleviating hypoxia. Cancer Cell. 2014; 26(5): 605-622.

[28]

Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004; 350(23): 2335-2342.

[29]

Jung K, Heishi T, Khan OF, et al. Ly6Clo monocytes drive immunosuppression and confer resistance to anti-VEGFR2 cancer therapy. J Clin Invest. 2017; 127(8): 3039-3051.

[30]

Morad G, Helmink BA, Sharma P, Wargo JA. Hallmarks of response, resistance, and toxicity to immune checkpoint blockade. Cell. 2022; 185(3): 576.

[31]

Asrir A, Tardiveau C, Coudert J, et al. Tumor-associated high endothelial venules mediate lymphocyte entry into tumors and predict response to PD-1 plus CTLA-4 combination immunotherapy. Cancer Cell. 2022; 40(3): 318-334.e9.

[32]

Gabriel EM, Kim M, Fisher DT, et al. A pilot trial of intravital microscopy in the study of the tumor vasculature of patients with peritoneal carcinomatosis. Sci Rep. 2021; 11(1): 4946.

[33]

De Biase G, Garcia DP, Bohnen A, Quinones-Hinojosa A. Perioperative management of patients with glioblastoma. Neurosurg Clin N Am. 2021; 32(1): 1-8.

[34]

Morato NM, Brown HM, Garcia D, et al. High-throughput analysis of tissue microarrays using automated desorption electrospray ionization mass spectrometry. Sci Rep. 2022; 12(1):18851.

[35]

Shireman JM, Cheng L, Goel A, et al. Spatial transcriptomics in glioblastoma: is knowing the right zip code the key to the next therapeutic breakthrough? Front Oncol. 2023; 13:1266397.

[36]

Koay JM, Michaelides L, Moniz-Garcia DP, et al. Repeated surgical resections for management of high-grade glioma and its impact on quality of life. J Neurooncol. 2024; 167(2): 267-273.

[37]

Quinones-Hinojosa A, Basil A, Moniz-Garcia D, et al. From the operating room to the laboratory: the role of the neuroscience tissue biorepository in the clinical, translational, and basic science research pipeline. Mayo Clin Proc. 2024;99:229-240.

[38]

Moniz-Garcia D, Bojaxhi E, Borah BJ, et al. Awake craniotomy program implementation. JAMA Netw Open. 2024; 7(1):e2352917.

[39]

Shamul JG, Wang Z, Gong H, et al. Meta-analysis of the make-up and properties of in vitro models of the healthy and diseased blood‒brain barrier. Nat Biomed Eng. 2024.

[40]

Maity S, Bhuyan T, Jewell C, et al. Recent developments in glioblastoma-on-a-chip for advanced drug screening applications. Small. 2025; 21(1):e2405511.

[41]

Kiesslich R, Gossner L, Goetz M, et al. In vivo histology of Barrett's esophagus and associated neoplasia by confocal laser endomicroscopy. Clin Gastroenterol Hepatol. 2006; 4(8): 979-987.

[42]

Nakao M, Yoshida S, Tanaka S, et al. Optical biopsy of early gastroesophageal cancer by catheter-based reflectance-type laser-scanning confocal microscopy. J Biomed Opt. 2008; 13(5):054043.

[43]

Xie XJ, Li CQ, Zuo XL. Differentiation of colonic polyps by confocal laser endomicroscopy. Endoscopy. 2011; 43(2): 87-93.

[44]

Gabriel EM, Kim M, Fisher DT, et al. Dynamic control of tumor vasculature improves antitumor responses in a regional model of melanoma. Sci Rep. 2020; 10(1):13245.

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2025 The Author(s). Clinical and Translational Discovery published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.

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