Crosstalk Between Mesenchymal Stromal Cells and Tumor-Associated Macrophages in Gastric Cancer

Abstract

Tumor microenvironment (TME) consisting of distinct cell types including stromal cells and immune cells has recently emerged as a pivotal player in tumor development and progression. Mesenchymal stromal cells (MSCs) and tumor-associated macrophages (TAMs) are two representative cells in the TME with plastic properties. This review will focus on the evolution of phenotypes and functions of either MSCs or TAMs, which is "educated" by the TME, as well as interactions between MSCs and TAMs contributing to the distinct stages of tumor biology in gastric cancer. MSCs exert immunoregulatory effects on macrophages and polarize them toward M2-like TAMs, via cell-cell contact and paracrine or extracellular vesicle (EV) transfer mechanism. In turn, M2-TAMs modulate the transition of "naive" MSCs into tumor-derived MSCs, which possess a more potent pro-tumor role than the parent. Moreover, the cross talk between MSCs and TAMs could contribute to cancer biology by inducing the EMT process, metastasis, immune invasion, and immunotherapy resistance in cancer cells. However, molecular mechanisms underlying interactions between MSCs and TAMs in gastric cancer progression need to be thoroughly elucidated, which may provide attractive targets for making promising novel strategies for gastric cancer therapy.

Keywords: extracellular vesicles; gastric cancer; mesenchymal stromal cells; tumor microenvironment; tumor-associated macrophages.

FIGURE 1

Cross talk between tumor-derived MSCs and TAMs, and its contribution to the development and progression of gastric cancer within the TME. By cell-to-cell contact, paracrine effect, or EV transfer, tumor-derived MSCs induce the polarization of macrophages to obtain an M2-like phenotype, which is termed as TAMs and can promote the proliferation, invasion, and metastasis of gastric cancer cells. In turn, M2 TAMs can trigger the transition of naïve BM-MSCs into tumor-derived MSCs, which also play a tumor-supportive role in gastric cancer.

FIGURE 2

The regulating effects of MSC-TAM interaction on the fate of gastric cancer cells. In the TME of gastric cancer, cross talk between MSCs and TAMs provides a pro-tumor microenvironment by promoting the EMT process and metastasis of gastric cancer cells, as well as the immune escape and immunotherapy resistance in gastric cancer treatments.