2023
DOI: 10.3390/cells12060846
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Heterogeneity of Cholangiocarcinoma Immune Biology

Abstract: Cholangiocarcinomas (CCAs) are aggressive tumors arising along the biliary tract epithelium, whose incidence and mortality are increasing. CCAs are highly desmoplastic cancers characterized by a dense tumor microenvironment (TME), in which each single component plays a fundamental role in shaping CCA initiation, progression and resistance to therapies. The crosstalk between cancer cells and TME can affect the recruitment, infiltration and differentiation of immune cells. According to the stage of the disease a… Show more

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Cited by 14 publications
(8 citation statements)
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“…TILs are the most important components of the tumor immune microenvironment. Many studies have proposed TILs as crucial prognostic and efficacy predictive indicators, including CD3 + , CD4 + , and CD8 + lymphocytes 7,36–42 . Previous studies have suggested that CD8 + T‐cell infiltration is related to improved survival in patients receiving immunochemotherapy 7,40,42 .…”
Section: Discussionmentioning
confidence: 99%
“…TILs are the most important components of the tumor immune microenvironment. Many studies have proposed TILs as crucial prognostic and efficacy predictive indicators, including CD3 + , CD4 + , and CD8 + lymphocytes 7,36–42 . Previous studies have suggested that CD8 + T‐cell infiltration is related to improved survival in patients receiving immunochemotherapy 7,40,42 .…”
Section: Discussionmentioning
confidence: 99%
“…The hypoxic and hypovascularized CCA microenvironment and extensive desmoplasia furthermore constitute a physical barrier that compromises the delivery of chemotherapeutics, further complicating treatment decisions and patient management [20]. Indeed, reciprocal crosstalk between CAFs (and other immune cells in CCA) promotes tumor progression, tissue invasion and metastasis by stimulating the expression of inflammatory and pro-tumorigenic factors, immunosuppressive cytokines and the activation of stemness pathways [39], the latter likely through the 5-LO/LTB4-BLT2 axis and TGF-β signaling [30][31][32][33][34][35][36][37][38][39][40]. In other tumor types, this dense desmoplastic stroma is the consequence of coordinated phenotypic changes in several resident populations (i.e., fibroblasts, macrophages, adipocytes, endothelial cells) and is mechanistically associated with a reduction in CD36 expression [41].…”
Section: The Desmoplastic Tumor Microenvironment In Ccamentioning
confidence: 99%
“…There are approximately 14 different CAF phenotypes in human tumors. Two in particular, the inflammatory (iCAFs) and the myofibroblastic (myCAFs) variants, are prominent among the six subtypes of CAFs evident in CCA [17,34,39]. Although there is some phenotypic plasticity evident [43], the iCAFs and myCAFs express a restricted repertoire of biomarkers [44].…”
Section: Caf Subtypes In Cholangiocarcinomamentioning
confidence: 99%
“…The presence of a good immune infiltrate, such as tumor-infiltrating lymphocytes (TILs), correlates with a good prognosis in a large spectrum of solid tumors, including GI cancers [ 90 , 91 ]. However, pro-tumor immune populations, including TAM2, MDSCs, neutrophil N2, and Tregs, are highly present in these tumors [ 92 , 93 , 94 ]. Each one contributes to tumor aggressiveness through the secretion of inflammatory cytokines and chemokines, key effector molecules such as MMPs, prostaglandin E2 (PGE2), and TGF-β.…”
Section: Tumor Microenvironment In Promoting Cancer Cells Migration A...mentioning
confidence: 99%