Tumor microenvironment highlighting tumor-associated macrophages and immune cells

Giulio Lodetti Zangrandi , Dilruba Tirpanlar , Mirella Pastore , Cristiana Soldani , Ana Lleo , Chiara Raggi

Hepatoma Research ›› 2023, Vol. 9 : 32

PDF
Hepatoma Research ›› 2023, Vol. 9:32 DOI: 10.20517/2394-5079.2023.32
Review

Tumor microenvironment highlighting tumor-associated macrophages and immune cells

Author information +
History +
PDF

Abstract

Cholangiocarcinoma (CCA) grows within a highly desmoplastic microenvironment, exhibiting a continuous interconnection with the immune infiltrate, which is characterized by an abundance of immune cells, including natural killer cells, T lymphocytes, and macrophages. The presence of inflammatory cells within the tumor microenvironment plays a crucial role in determining the aggressiveness and growth of CCA. The immune cell population engages in diverse and dynamic interactions with cancer cells. The balance of different subpopulations within CCA can generate varying responses, either inhibiting or promoting tumoral progression. The purpose of this review is to offer a comprehensive overview of the role of various immune infiltrate subpopulations within the tumor microenvironment, with a particular focus on the actions of tumor-associated macrophages (TAMs) and their critical regulation in the development and progression of CCA. TAMs play vital roles in maintaining homeostasis, facilitating tissue repair, and contributing to immune responses due to their significant functional diversity. Macrophages are present in numerous types of cancer, and their emerging role has also been observed in CCA. Recognizing and attaining a deeper comprehension of the intricate interplay between infiltrating immune cells and CCA cells is essential to identify new opportunities to advance treatment strategies.

Keywords

Cholangiocarcinoma (CCA) / immune infiltrate / tumor-associated macrophages (TAMs) / macrophage / macrophage polarization / tumor microenvironment

Cite this article

Download citation ▾
Giulio Lodetti Zangrandi, Dilruba Tirpanlar, Mirella Pastore, Cristiana Soldani, Ana Lleo, Chiara Raggi. Tumor microenvironment highlighting tumor-associated macrophages and immune cells. Hepatoma Research, 2023, 9: 32 DOI:10.20517/2394-5079.2023.32

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

Razumilava N.Cholangiocarcinoma.Lancet2014;383:2168-79.

[2]

Cadamuro M,Zhang X.Tumor microenvironment and immunology of cholangiocarcinoma.Hepatoma Res2022;8:11

[3]

Bertuccio P,Carioli G.Global trends in mortality from intrahepatic and extrahepatic cholangiocarcinoma.J Hepatol2019;71:104-14.

[4]

Yao KJ,Parekh N,Moss RA.Increasing mortality in the United States from cholangiocarcinoma: an analysis of the National Center for Health Statistics Database.BMC Gastroenterol2016;16:117 PMCID:PMC5031355

[5]

Strijker M,van der Geest LG.Dutch Pancreatic Cancer GroupTreatment and survival of resected and unresected distal cholangiocarcinoma: a nationwide study.Acta Oncol2019;58:1048-55

[6]

Khan SA,Brandi G.Cholangiocarcinoma: epidemiology and risk factors.Liver Int2019;39 Suppl 1:19-31

[7]

Lendvai G,Illyés I.Cholangiocarcinoma: classification, histopathology and molecular carcinogenesis.Pathol Oncol Res2020;26:3-15.

[8]

Kendall T,Gaudio E.Anatomical, histomorphological and molecular classification of cholangiocarcinoma.Liver Int2019;39 Suppl 1:7-18.

[9]

Gerber TS,Bartsch F.Integrative analysis of intrahepatic cholangiocarcinoma subtypes for improved patient stratification: clinical, pathological, and radiological considerations.Cancers2022;14:3156 PMCID:PMC9264781

[10]

Nakeeb A,Sohn TA.Cholangiocarcinoma. A spectrum of intrahepatic, perihilar, and distal tumors.Ann Surg1996;224:463-73; discussion 473 PMCID:PMC1235406

[11]

Nagtegaal ID,Klimstra D.WHO Classification of Tumours Editorial BoardThe 2019 WHO classification of tumours of the digestive system.Histopathology2020;76:182-8 PMCID:PMC7003895

[12]

Komuta M,Vandecaveye V.Histological diversity in cholangiocellular carcinoma reflects the different cholangiocyte phenotypes.Hepatology2012;55:1876-88

[13]

Aishima S.Pathogenesis and classification of intrahepatic cholangiocarcinoma: different characters of perihilar large duct type versus peripheral small duct type.J Hepatobiliary Pancreat Sci2015;22:94-100

[14]

Nakanuma Y,Harada K,Xu J.Pathological classification of intrahepatic cholangiocarcinoma based on a new concept.World J Hepatol2010;2:419-27 PMCID:PMC3010511

[15]

Song G,Meng L.Single-cell transcriptomic analysis suggests two molecularly subtypes of intrahepatic cholangiocarcinoma.Nat Commun2022;13:1642. PMCID:PMC9114109

[16]

Buettner S,IJzermans JN.Intrahepatic cholangiocarcinoma: current perspectives.Onco Targets Ther2017;10:1131-42. PMCID:PMC5328612

[17]

DeOliveira ML,Cameron JL.Cholangiocarcinoma: thirty-one-year experience with 564 patients at a single institution.Ann Surg2007;245:755-62. PMCID:PMC1877058

[18]

Banales JM,Lamarca A.Cholangiocarcinoma 2020: the next horizon in mechanisms and management.Nat Rev Gastroenterol Hepatol2020;17:557-88 PMCID:PMC7447603

[19]

Nakanuma Y.Pathologic classification of cholangiocarcinoma: new concepts.Best Pract Res Clin Gastroenterol2015;29:277-93

[20]

Liau JY,Yuan RH,Lee HJ.Morphological subclassification of intrahepatic cholangiocarcinoma: etiological, clinicopathological, and molecular features.Mod Pathol2014;27:1163-73

[21]

Carpino G,Folseraas T.Neoplastic transformation of the peribiliary stem cell niche in cholangiocarcinoma arisen in primary sclerosing cholangitis.Hepatology2019, 69:622-38.

[22]

Arai Y,Hosoda F.Fibroblast growth factor receptor 2 tyrosine kinase fusions define a unique molecular subtype of cholangiocarcinoma.Hepatology2014;59:1427-34

[23]

Borger DR,Fan KC.Frequent mutation of isocitrate dehydrogenase (IDH)1 and IDH2 in cholangiocarcinoma identified through broad-based tumor genotyping.Oncologist2012;17:72-9 PMCID:PMC3267826

[24]

Petrick JL,Altekruse SF.Risk factors for intrahepatic and extrahepatic cholangiocarcinoma in the United States: a population-based study in SEER-Medicare.PLoS One2017;12:e0186643 PMCID:PMC5648218

[25]

Cardinale V,Torrice A.Intra-hepatic and extra-hepatic cholangiocarcinoma: new insight into epidemiology and risk factors.World J Gastrointest Oncol2010;2:407-16 PMCID:PMC3000454

[26]

El-Serag HB,Landgren O.Risk of hepatobiliary and pancreatic cancers after hepatitis C virus infection: a population-based study of U.S. veterans.Hepatology2009;49:116-23 PMCID:PMC2719902

[27]

Abdalla EK,Lauwers GY.Monolobar Caroli's disease and cholangiocarcinoma.HPB Surg1999;11:271-6; discussion 276

[28]

Mehta TI,Fung BM.Geoepidemiologic variation in outcomes of primary sclerosing cholangitis.World J Hepatol2020;12:116-24. PMCID:PMC7336294

[29]

Choi BI,Hong ST.Clonorchiasis and cholangiocarcinoma: etiologic relationship and imaging diagnosis.Clin Microbiol Rev2004;17:540-52, table of contents PMCID:PMC452546

[30]

La Vecchia C,Bertuccio P.Trends in alcohol consumption in Europe and their impact on major alcohol-related cancers.Eur J Cancer Prev, 2014, 23:319-22

[31]

Michelotti GA,Diehl AM.NAFLD, NASH and liver cancer.Nat Rev Gastroenterol Hepatol2013;10:656-65

[32]

Wise C,Perry BF,McNeal M.Mechanisms of biliary carcinogenesis and growth.World J Gastroenterol2008;14:2986-9. PMCID:PMC2712163

[33]

Andersen JB.Genetic profiling of intrahepatic cholangiocarcinoma.Curr Opin Gastroenterol2012;28:266-72 PMCID:PMC4017233

[34]

Andersen JB.Molecular pathogenesis of intrahepatic cholangiocarcinoma.J Hepatobiliary Pancreat Sci2015;22:101-13

[35]

Höpfner M,Scherübl H.Growth factor receptors and related signalling pathways as targets for novel treatment strategies of hepatocellular cancer.World J Gastroenterol2008;14:1-14 PMCID:PMC2673371

[36]

Andersen JB,Blechacz BR.Genomic and genetic characterization of cholangiocarcinoma identifies therapeutic targets for tyrosine kinase inhibitors.Gastroenterology2012;142:1021-1031.e15 PMCID:PMC3413201

[37]

Nakamura H,Totoki Y.Genomic spectra of biliary tract cancer.Nat Genet2015;47:1003-10

[38]

Testa U,Castelli G.Cholangiocarcinoma: molecular abnormalities and cells of origin.Technol Cancer Res Treat2023;22:15330338221128689 PMCID:PMC9989414

[39]

Yang R,Shakoor K,Peng C.Insights into the role of STAT3 in intrahepatic cholangiocarcinoma (Review).Mol Med Rep2022;25:171 PMCID:PMC8971913

[40]

Grivennikov SI,Karin M.Immunity, inflammation, and cancer.Cell2010;140:883-99.

[41]

Balkwill FR,Hagemann T.The tumor microenvironment at a glance.J Cell Sci2012;125:5591-6

[42]

Zhou Z,Sun R.Tumor-associated neutrophils and macrophages interaction contributes to intrahepatic cholangiocarcinoma progression by activating STAT3.J Immunother Cancer2021;9:e001946 PMCID:PMC7949476

[43]

Høgdall D,Andersen JB.Desmoplastic tumor microenvironment and immunotherapy in cholangiocarcinoma.Trends Cancer2018;4:239-55.

[44]

Sirica AE.Desmoplastic stroma and cholangiocarcinoma: clinical implications and therapeutic targeting.Hepatology2014;59:2397-402. PMCID:PMC3975806

[45]

Badalamenti G,Incorvaia L.Role of tumor-infiltrating lymphocytes in patients with solid tumors: can a drop dig a stone?.Cell Immunol2019;343:103753.

[46]

Fabris L,Alpini G.The tumor microenvironment in cholangiocarcinoma progression.Hepatology2021;73 Suppl 1:75-85 PMCID:PMC7714713

[47]

Paijens ST,de Bruyn M.Tumor-infiltrating lymphocytes in the immunotherapy era.Cell Mol Immunol2021;18:842-59 PMCID:PMC8115290

[48]

Cao H,Dai M.Tumor microenvironment and its implications for antitumor immunity in cholangiocarcinoma: future perspectives for novel therapies.Int J Biol Sci2022;18:5369-90 PMCID:PMC9461676

[49]

Liu D,Czigany Z.The role of tumor-infiltrating lymphocytes in cholangiocarcinoma.J Exp Clin Cancer Res2022;41:127 PMCID:PMC8988317

[50]

Walker LS.Treg and CTLA-4: two intertwining pathways to immune tolerance.J Autoimmun2013;45:49-57 PMCID:PMC3989116

[51]

Alvisi G,Soldani C.Multimodal single-cell profiling of intrahepatic cholangiocarcinoma defines hyperactivated Tregs as a potential therapeutic target.J Hepatol2022;77:1359-72

[52]

Kitano Y,Yamashita YI.Tumour-infiltrating inflammatory and immune cells in patients with extrahepatic cholangiocarcinoma.Br J Cancer2018;118:171-80 PMCID:PMC5785749

[53]

Malenica I,Lleo A.Molecular and immunological characterization of biliary tract cancers: a paradigm shift towards a personalized medicine.Cancers2020; 12:2190 PMCID:PMC7464597

[54]

Philip M.CD8+ T cell differentiation and dysfunction in cancer.Nat Rev Immunol2022;22:209-23 PMCID:PMC9792152

[55]

Loeuillard E,Gores GJ.Immunobiology of cholangiocarcinoma.JHEP Rep2019;1:297-311 PMCID:PMC7001542

[56]

Shen M,Wang J,Ren X.Positive and negative functions of B lymphocytes in tumors.Oncotarget2016;7:55828-39

[57]

Chen Z,Yan J.PNOC expressed by B cells in cholangiocarcinoma was survival related and LAIR2 could be a t cell exhaustion biomarker in tumor microenvironment: characterization of immune microenvironment combining single-cell and bulk sequencing technology.Front Immunol2021;12:647209 PMCID:PMC8024580

[58]

Morvan MG.NK cells and cancer: you can teach innate cells new tricks.Nat Rev Cancer2016;16:7-19

[59]

Martín-Sierra C,Laranjeira P.Functional and phenotypic characterization of tumor-infiltrating leukocyte subsets and their contribution to the pathogenesis of hepatocellular carcinoma and cholangiocarcinoma.Transl Oncol2019;12:1468-79 PMCID:PMC6712279

[60]

Mikulak J,Oriolo F,Mavilio D.Hepatic natural killer cells: organ-specific sentinels of liver immune homeostasis and physiopathology.Front Immunol2019;10:946 PMCID:PMC6502999

[61]

Polidoro MA,Cazzetta V.Tumor microenvironment in primary liver tumors: a challenging role of natural killer cells.World J Gastroenterol2020;26:4900-18 PMCID:PMC7476172

[62]

Jung IH,Yoo DK.In vivo study of natural killer (NK) cell cytotoxicity against cholangiocarcinoma in a nude mouse model.In Vivo2018;32:771-81.

[63]

Carnevale G,Cardinale V.Activation of Fas/FasL pathway and the role of c-FLIP in primary culture of human cholangiocarcinoma cells.Sci Rep2017;7:14419 PMCID:PMC5663931

[64]

Giese MA,Huttenlocher A.Neutrophil plasticity in the tumor microenvironment.Blood2019;133:2159-67

[65]

Masucci MT,Del Vecchio S.The emerging role of neutrophil extracellular traps (NETs) in tumor progression and metastasis.Front Immunol2020;11:1749 PMCID:PMC7524869

[66]

Masucci MT,Carriero MV.Tumor associated neutrophils. Their role in tumorigenesis, metastasis, prognosis and therapy.Front Oncol2019;9:1146. PMCID:PMC6874146

[67]

Zhou SL,Zhou ZJ.CXCL5 contributes to tumor metastasis and recurrence of intrahepatic cholangiocarcinoma by recruiting infiltrative intratumoral neutrophils.Carcinogenesis2014;35:597-605

[68]

Ge MY,Pan Y.Assessment of the prognostic value of the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in perihilar cholangiocarcinoma patients following curative resection: a multicenter study of 333 patients.Front Oncol2022;12:1104810 PMCID:PMC9845724

[69]

Lin G,Li S.Elevated neutrophil-to-lymphocyte ratio is an independent poor prognostic factor in patients with intrahepatic cholangiocarcinoma.Oncotarget2016;7:50963-71

[70]

Anderson DA 3rd,Briseño CG.Development, diversity, and function of dendritic cells in mouse and human.Cold Spring Harb Perspect Biol2018;10:a028613 PMCID:PMC6211386

[71]

Spranger S,Horton B.Tumor-Residing Batf3 dendritic cells are required for effector T cell trafficking and adoptive T cell therapy.Cancer Cell2017;31:711-723.e4 PMCID:PMC5650691

[72]

Conrad C,Wang YH.Plasmacytoid dendritic cells promote immunosuppression in ovarian cancer via ICOS costimulation of Foxp3+ T-regulatory cells.Cancer Res2012;72:5240-9 PMCID:PMC3652570

[73]

Thepmalee C,Junking M,Yenchitsomanus PT.Inhibition of IL-10 and TGF-β receptors on dendritic cells enhances activation of effector T-cells to kill cholangiocarcinoma cells.Hum Vaccin Immunother2018;14:1423-31. PMCID:PMC6037468

[74]

Cazzetta V,Carenza C,Mikulak J.Natural killer-dendritic cell interactions in liver cancer: implications for immunotherapy.Cancers2021;13:2184 PMCID:PMC8124166

[75]

Ma C,Greten TF.MDSCs in liver cancer: A critical tumor-promoting player and a potential therapeutic target.Cell Immunol2021;361:104295. PMCID:PMC7882059

[76]

Veglia F,Gabrilovich DI.Myeloid-derived suppressor cells in the era of increasing myeloid cell diversity.Nat Rev Immunol2021;21:485-98 PMCID:PMC7849958

[77]

Xu XD,Wang M.Circulating myeloid-derived suppressor cells in patients with pancreatic cancer.Hepatobiliary Pancreat Dis Int2016;15:99-105.

[78]

Gu FM,Shi GM.Intratumoral IL-17+ cells and neutrophils show strong prognostic significance in intrahepatic cholangiocarcinoma.Ann Surg Oncol2012;19:2506-14

[79]

Mosser DM.Exploring the full spectrum of macrophage activation.Nat Rev Immunol2008;8:958-69 PMCID:PMC2724991

[80]

Wynn TA,Pollard JW.Macrophage biology in development, homeostasis and disease.Nature2013;496:445-55 PMCID:PMC3725458

[81]

Anderson NM.The tumor microenvironment.Curr Biol2020;30:R921-5. PMCID:PMC8194051

[82]

Peiseler M.Macrophages play an essential role in trauma-induced sterile inflammation and tissue repair.Eur J Trauma Emerg Surg2018;44:335-49.

[83]

Akashi K,Miyamoto T.A clonogenic common myeloid progenitor that gives rise to all myeloid lineages.Nature2000;404:193-7.

[84]

Fogg DK,Miled C.A clonogenic bone marrow progenitor specific for macrophages and dendritic cells.Science2006;311:83-7

[85]

Hettinger J,Hansson J.Origin of monocytes and macrophages in a committed progenitor.Nat Immunol2013;14:821-30

[86]

Hamilton JA.Colony-stimulating factors in inflammation and autoimmunity.Nat Rev Immunol2008;8:533-44

[87]

Kumar A,Sanchez Ortiz A.GM-CSF: a double-edged sword in cancer immunotherapy.Front Immunol2022;13:901277. PMCID:PMC9294178

[88]

Gautier EL,Miller J.Immunological Genome ConsortiumGene-expression profiles and transcriptional regulatory pathways that underlie the identity and diversity of mouse tissue macrophages.Nat Immunol2012;13:1118-28 PMCID:PMC3558276

[89]

Kim J.Tumor-Associated macrophages and neutrophils in tumor microenvironment.Mediators Inflamm2016;2016:6058147 PMCID:PMC4757693

[90]

Mantovani A,Sica A.Tumour-associated macrophages as a prototypic type II polarised phagocyte population: role in tumour progression.Eur J Cancer2004;40:1660-7

[91]

Sica A,Mantovani A.Cancer related inflammation: the macrophage connection.Cancer Lett2008;267:204-15

[92]

Hinshaw DC.The tumor microenvironment innately modulates cancer progression.Cancer Res2019;79:4557-66 PMCID:PMC6744958

[93]

Salmaninejad A,Soltani A.Tumor-associated macrophages: role in cancer development and therapeutic implications.Cell Oncol2019;42:591-608.

[94]

Mills CD,Alt JM,Hill AM.M-1/M-2 macrophages and the Th1/Th2 paradigm.J Immunol2000;164:6166-73

[95]

Biswas SK.Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm.Nat Immunol2010;11:889-96

[96]

Billiau A.Interferon-gamma: a historical perspective.Cytokine Growth Factor Rev2009;20:97-113

[97]

Fleetwood AJ,Hamilton JA.Granulocyte-macrophage colony-stimulating factor (CSF) and macrophage CSF-dependent macrophage phenotypes display differences in cytokine profiles and transcription factor activities: implications for CSF blockade in inflammation.J Immunol2007;178:5245-52.

[98]

Zhu J,Zhou BP,Liu J.The role of tumor associated macrophages in the tumor microenvironment: mechanism and functions.Anticancer Agents Med Chem2016;16:1133-41

[99]

Jayasingam SD,Thang TH,Ang KC.Evaluating the polarization of tumor-associated macrophages into M1 and M2 phenotypes in human cancer tissue: technicalities and challenges in routine clinical practice.Front Oncol2019;9:1512 PMCID:PMC6992653

[100]

Sica A,Mancino A.Macrophage polarization in tumour progression.Semin Cancer Biol2008;18:349-55

[101]

Gordon S.Alternative activation of macrophages: mechanism and functions.Immunity2010;32:593-604.

[102]

Tamura R,Yamamoto Y,Sasaki H.Dual role of macrophage in tumor immunity.Immunotherapy2018;10:899-909

[103]

Wu K,Li X.Redefining tumor-associated macrophage subpopulations and functions in the tumor microenvironment.Front Immunol2020;11:1731. PMCID:PMC7417513

[104]

de Sousa JR,Aarão TL.In situ expression of M2 macrophage subpopulation in leprosy skin lesions.Acta Trop2016;157:108-14.

[105]

Huang X,Fu M.Polarizing macrophages in vitro. In: Rousselet G, editor. Macrophages. New York: Springer; 2018. pp. 119-26. PMCID:PMC8875934

[106]

Yang L.Tumor-associated macrophages: from basic research to clinical application.J Hematol Oncol2017;10:58 PMCID:PMC5329931

[107]

Satoh T,Vandenbon A.The Jmjd3-Irf4 axis regulates M2 macrophage polarization and host responses against helminth infection.Nat Immunol2010;11:936-44

[108]

Kaler P,Klampfer L.Macrophage-derived IL-1beta stimulates Wnt signaling and growth of colon cancer cells: a crosstalk interrupted by vitamin D3.Oncogene2009;28:3892-902 PMCID:PMC2783659

[109]

Chen Y.Pivotal regulators of tissue homeostasis and cancer: macrophages.Exp Hematol Oncol2017;6:23 PMCID:PMC5549331

[110]

Martinez F O,Locati M.Transcriptional profiling of the human monocyte-to-macrophage differentiation and polarization: new molecules and patterns of gene expression.J Immunol2006;177:7303-7311

[111]

Caccamo N,Sireci G,Stassi G.Mechanisms underlying lineage commitment and plasticity of human γδ T cells.Cell Mol Immunol2013;10:30-4 PMCID:PMC4003171

[112]

O'Shea JJ.Mechanisms underlying lineage commitment and plasticity of helper CD4+ T cells.Science2010;327:1098-102 PMCID:PMC2997673

[113]

Qian B Z.Macrophage diversity enhances tumor progression and metastasis.Cell2010;141:39-51

[114]

De Palma M,Galli R.Tie2 identifies a hematopoietic lineage of proangiogenic monocytes required for tumor vessel formation and a mesenchymal population of pericyte progenitors.Cancer Cell2005;8:211-26.

[115]

Sica A.Altered macrophage differentiation and immune dysfunction in tumor development.J Clin Invest2007;117:1155-66 PMCID:PMC1857267

[116]

Condeelis J.Macrophages: obligate partners for tumor cell migration, invasion, and metastasis.Cell2006;124:263-6

[117]

Peinado H,Matei IR.Pre-metastatic niches: organ-specific homes for metastases.Nat Rev Cancer2017;17:302-17

[118]

Psaila B.The metastatic niche: adapting the foreign soil.Nat Rev Cancer2009;9:285-93 PMCID:PMC3682494

[119]

Peinado H,Lavotshkin S.Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET.Nat Med2012;18:883-91

[120]

Ojalvo LS,Condeelis JS.Gene expression analysis of macrophages that facilitate tumor invasion supports a role for Wnt-signaling in mediating their activity in primary mammary tumors.J Immunol2010;184:702-12. PMCID:PMC3226722

[121]

Mazzieri R,Moi D.Targeting the ANG2/TIE2 axis inhibits tumor growth and metastasis by impairing angiogenesis and disabling rebounds of proangiogenic myeloid cells.Cancer Cell2011;19:512-26.

[122]

Murdoch C,Coffelt SB.The role of myeloid cells in the promotion of tumour angiogenesis.Nat Rev Cancer2008;8:618-31

[123]

Lin EY,Gnatovskiy L.Macrophages regulate the angiogenic switch in a mouse model of breast cancer.Cancer Res2006;66:11238-46

[124]

Lewis C.Macrophage responses to hypoxia: implications for tumor progression and anti-cancer therapies.Am J Pathol2005;167:627-35 PMCID:PMC1698733

[125]

Murdoch C,Lewis CE.Mechanisms regulating the recruitment of macrophages into hypoxic areas of tumors and other ischemic tissues.Blood2004;104:2224-34

[126]

Talks KL,Gatter KC.The expression and distribution of the hypoxia-inducible factors HIF-1alpha and HIF-2alpha in normal human tissues, cancers, and tumor-associated macrophages.Am J Pathol2000;157:411-21 PMCID:PMC1850121

[127]

Vigano L,Franceschini B.Tumor-Infiltrating lymphocytes and macrophages in intrahepatic cholangiocellular carcinoma. Impact on prognosis after complete surgery.J Gastrointest Surg2019;23:2216-24

[128]

Donadon M,Cortese N.Macrophage morphology correlates with single-cell diversity and prognosis in colorectal liver metastasis.J Exp Med2020;217 PMCID:PMC7596819

[129]

Gazzillo A,Soldani C,Lleo A.Relationship between epithelial-to-mesenchymal transition and tumor-associated macrophages in colorectal liver metastases.Int J Mol Sci2022;23:16197. PMCID:PMC9783529

[130]

Fabris L,Mertens J.The tumour microenvironment and immune milieu of cholangiocarcinoma.Liver Int2019;39 Suppl 1:63-78.

[131]

Ziani L,Thiery J.Alteration of the antitumor immune response by cancer-associated fibroblasts.Front Immunol2018;9:414 PMCID:PMC5837994

[132]

Dwyer BJ,Gogoi-Tiwari J.TWEAK/Fn14 signalling promotes cholangiocarcinoma niche formation and progression.J Hepatol2021;74:860-72.

[133]

Ruffolo LI,Kuhlers PC.GM-CSF drives myelopoiesis, recruitment and polarisation of tumour-associated macrophages in cholangiocarcinoma and systemic blockade facilitates antitumour immunity.Gut2022;71:1386-98. PMCID:PMC8857285

[134]

Pak JH,Jeon BY,Yoo WG.Cytokine production in cholangiocarcinoma cells in response to clonorchis sinensis excretory-secretory products and their putative protein components.Korean J Parasitol2019;57:379-87. PMCID:PMC6753296

[135]

Vaeteewoottacharn K,Pothipan P.Attenuation of CD47-SIRPα signal in cholangiocarcinoma potentiates tumor-associated macrophage-mediated phagocytosis and suppresses intrahepatic metastasis.Transl Oncol2019;12:217-25.

[136]

Kim EM,Yi MH,Sohn WM.Clonorchis sinensis antigens alter hepatic macrophage polarization in vitro and in vivo.PLoS Negl Trop Dis2017;11:e0005614 PMCID:PMC5460902

[137]

Bingle L,Lewis CE.The role of tumour-associated macrophages in tumour progression: implications for new anticancer therapies.J Pathol2002;196:254-65

[138]

Hasita H,Okabe H.Significance of alternatively activated macrophages in patients with intrahepatic cholangiocarcinoma.Cancer Sci2010;101:1913-9

[139]

Sun D,Dong P.M2-polarized tumor-associated macrophages promote epithelial-mesenchymal transition via activation of the AKT3/PRAS40 signaling pathway in intrahepatic cholangiocarcinoma.J Cell Biochem2020;121:2828-38.

[140]

Yuan D,Berger E.Kupffer cell-derived Tnf triggers cholangiocellular tumorigenesis through jnk due to chronic mitochondrial dysfunction and ROS.Cancer Cell2017;31:771-789.e6 PMCID:PMC7909318

[141]

Boulter L,Kendall TJ.WNT signaling drives cholangiocarcinoma growth and can be pharmacologically inhibited.J Clin Invest2015;125:1269-85. PMCID:PMC4362247

[142]

Raggi C,Sica A.Cholangiocarcinoma stem-like subset shapes tumor-initiating niche by educating associated macrophages.J Hepatol2017;66:102-15 PMCID:PMC5522599

[143]

Johnson DB,Moslehi JJ.Immune-checkpoint inhibitors: long-term implications of toxicity.Nat Rev Clin Oncol2022;19:254-67 PMCID:PMC8790946

[144]

Ilyas SI,Goyal L.Cholangiocarcinoma-novel biological insights and therapeutic strategies.Nat Rev Clin Oncol2023;20:470-86

[145]

Lamarca A,Goyal L.How I treat biliary tract cancer.ESMO Open2022;7:100378 PMCID:PMC8762076

[146]

Maio M,Manzyuk L.Pembrolizumab in microsatellite instability high or mismatch repair deficient cancers: updated analysis from the phase II KEYNOTE-158 study.Ann Oncol2022;33:929-38

[147]

Food and Drug Administration US Food and Drug Administration. FDA grants accelerated approval to pembrolizumab for first tissue/site agnostic indication; 2017.

[148]

Food and Drug Administration US Food and Drug Administration. FDA approves pembrolizumab for adults and children with TMB-H solid tumors; 2020. PMCID:PMC8416776

[149]

Piha-Paul SA,Ueno M.Efficacy and safety of pembrolizumab for the treatment of advanced biliary cancer: results from the KEYNOTE-158 and KEYNOTE-028 studies.Int J Cancer2020;147:2190-8

[150]

Food and Drug Administration US Food and Drug Administration. FDA D.I.S.C.O. burst edition: FDA approval of Imfinzi (durvalumab) for adult patients with locally advanced or metastatic biliary tract cancer. Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-disco-burst-edition-fda-approval-imfinzi-durvalumab-adult-patients-locally-advanced-or [Last accessed on 28 Jul 2023]

[151]

NCCN National Comprehensive Cancer Network. NCCN guidelines: hepatobiliary cancer. Available from: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1438 [Last accessed on 28 Jul 2023]

[152]

June CH.Chimeric antigen receptor therapy.N Engl J Med2018;379:64-73 PMCID:PMC7433347

[153]

Guo Y,Liu Y.Phase I study of chimeric antigen receptor-modified T Cells in patients with EGFR-Positive advanced biliary tract cancers.Clin Cancer Res2018;24:1277-86

[154]

Supimon K,Sujjitjoon J.Anti-mucin 1 chimeric antigen receptor T cells for adoptive T cell therapy of cholangiocarcinoma.Sci Rep2021;11:6276 PMCID:PMC7973425

[155]

Sangsuwannukul T,Sujjitjoon J.Anti-tumour effect of the fourth-generation chimeric antigen receptor T cells targeting CD133 against cholangiocarcinoma cells.Int Immunopharmacol2020;89:107069.

[156]

Greten TF,Bardeesy N.Immunology and immunotherapy of cholangiocarcinoma.Nat Rev Gastroenterol Hepatol2023;20:349-65.

[157]

Loeuillard E,Buckarma E.Targeting tumor-associated macrophages and granulocytic myeloid-derived suppressor cells augments PD-1 blockade in cholangiocarcinoma.J Clin Invest2020;130:5380-96

[158]

Diggs LP,Ma C.CD40-mediated immune cell activation enhances response to anti-PD-1 in murine intrahepatic cholangiocarcinoma.J Hepatol2021;74:1145-54 PMCID:PMC9662232

[159]

Zhou M,Lu S.Tumor-associated macrophages in cholangiocarcinoma: complex interplay and potential therapeutic target.EBioMedicine2021;67:103375 PMCID:PMC8134032

PDF

146

Accesses

0

Citation

Detail

Sections
Recommended

/