Epigenetic mechanisms driving tumor supportive microenvironment differentiation and function: a role in cancer therapy?

The tumor microenvironment (TME) plays a central role in tumor development and drug resistance. Within TME, the stromal cell subset, called cancer-associated fibroblasts, is a heterogeneous population originating from poorly characterized precursors. Since cancer-associated fibroblasts do not acquire somatic mutations, other mechanisms like epigenetic regulation, could be involved in the development of these cells and in the acquisition of tumor supportive phenotypes. Moreover, such epigenetic modulations have been correlated to the emergence of an immunosuppressive microenvironment facilitating tumor evasion. These findings underline the need to deepen our knowledge on epigenetic mechanisms driving TME development and function, and to understand the impact of epigenetic drugs that could be used in future to target both tumor cells and their TME.