DNA methylation in the tumor microenvironment

Abstract

The tumor microenvironment (TME) plays an important role in supporting cancer progression. The TME is composed of tumor cells, the surrounding tumor-associated stromal cells, and the extracellular matrix (ECM). Crosstalk between the TME components contributes to tumorigenesis. Recently, one of our studies showed that pancreatic ductal adenocarcinoma (PDAC) cells can induce DNA methylation in cancer-associated fibroblasts (CAFs), thereby modifying tumor-stromal interactions in the TME, and subsequently creating a TME that supports tumor growth. Here we summarize recent studies about how DNA methylation affects tumorigenesis through regulating tumor-associated stromal components including fibroblasts and immune cells. We also discuss the potential for targeting DNA methylation for the treatment of cancers.

Keywords: Tumor microenvironment (TME); DNA methylation; Cancer-associated fibroblasts; Cancer-associated immune cells; Epigenetic therapy.

Fig. 1

Schematic representation of the TME A typical tumor microenvironment (TME) is composed mainly of cancer cells, cancer-associated fibroblasts (CAFs), multiple types of immune cells (T lymphocytes, B cells, natural killer (NK) cells, macrophages, and antigen presenting cells), vessels, and extracellular matrix (ECM)

Fig. 2

Epigenetic regulation, such as histone modification, non-coding RNA regulation, and DNA methylation, leads to different gene expressions in the tumor microenvironment (TME)