MiRNAs as Regulators of Immune Cells in the Tumor Microenvironment of Ovarian Cancer

Abstract

Ovarian cancer is one of the leading causes of cancer deaths among women. There is an ongoing need to develop new biomarkers and targeted therapies to improve patient outcomes. One of the most critical research areas in ovarian cancer is identifying tumor microenvironment (TME) functions. TME consists of tumor-infiltrating immune cells, matrix, endothelial cells, pericytes, fibroblasts, and other stromal cells. Tumor invasion and growth depend on the multifactorial crosstalk between tumor cells and immune cells belonging to the TME. MiRNAs, which belong to non-coding RNAs that post-transcriptionally control the expression of target genes, regulate immune responses within the TME, shaping the landscape of the intrinsic environment of tumor cells. Aberrant expression of miRNAs may lead to the pathological dysfunction of signaling pathways or cancer cell-regulatory factors. Cell-to-cell communication between infiltrating immune cells and the tumor may depend on exosomes containing multiple miRNAs. MiRNAs may exert both immunosuppressive and immunoreactive responses, which may cause cancer cell elimination or survival. In this review, we highlighted recent advances in the field of miRNAs shaping the landscape of immune cells in the TME.

Keywords: miRNAs; ovarian cancer; tumor microenvironment.

Figure 1

miRNAs regulate both TME and tumor, being part of a multilayered and mutual network between cancer and immune cells. Tumor-derived exosomes containing miRNAs modulate the actions of immune cells in the TME. Up- or downregulation of certain miRNAs in immune cells being part of the TME also affects tumor growth and progression. Such phenomena may cause immunotolerance or tumor elimination. Immune cells: natural killer cells—NK cells; myeloid-derived suppressor cells—MDSC; regulatory T cells—Treg; CD8⁺ T cells—T cytotoxic; dendritic cells—DC; cancer-associated fibroblasts—CAFs.