Crosstalk between cancer cell plasticity and immune microenvironment in cholangiocarcinoma

Abstract

Cholangiocarcinoma (CCA) is a highly aggressive tumor of the biliary tree characterized by an intense desmoplastic tumor microenvironment (TME). To date, treatment of CCA remains challenging; tumor resection is the only curative treatment with a high recurrence probability. Besides resection, therapeutic options have moved forward with the advent of immunotherapies, but these remain limited and low effective. Our knowledge about the cellular interplays in CCA is still fragmentary. An area is currently emerging regarding the potential role of cell plasticity in the genesis of an immunosuppressive microenvironment. The cancer cells’ ability to acquire stemness properties and to disseminate through an epithelial-mesenchymal transition (EMT) shape a tumor immune microenvironment that supports cancer progression by attracting immunosuppressive cells including myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), M2 macrophages, and by increasing the expression of inhibitory immune checkpoints such as PD-1/PD-L-1. EMT-inducing transcription factors (EMT-TF) have recently emerged as regulators of tumor immunity by creating an immunosuppressive microenvironment. This review delves into the molecular mechanisms underlying the existing links between EMT/stemness and tumor immune microenvironment, as well as the last discoveries in CCA.

Keywords

Cancer cell plasticity / epithelial-mesenchymal transition / cancer stem cells / EMT-TF / immune evasion

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