Role of chemokines in the crosstalk between tumor and tumor-associated macrophages

Abstract

Tumor microenvironment (TME) consists of a dynamic network of non-tumoral stromal cells, including cancer-associated fibroblasts, endothelial cells, tumor-associated macrophages (TAMs), B and T cells. In the TME, TAMs support tumor initiation, progression, invasion and metastasis by promoting angiogenesis and immunosuppression of the tumor cells. There is close crosstalk between TAMs and tumor cells. Notably, chemokines are a significant messenger mediating the crosstalk between tumor cells and TAMs. TAMs can promote tumor progression via secretion of chemokines. Various chemokines secreted by tumors are involved in the generation and polarization of TAMs, the infiltration of TAMs in tumors, and the development of TAMs' suppressive function. This paper reviews CCL2-CCR2, CCL3/5-CCR5, CCL15-CCR1, CCL18-CCR8, CX3CL1/CCL26-CX3CR1, CXCL8-CXCR1/2, CXCL12-CXCR4/CXCR7 signaling pathways, their role in the recruitment, polarization and exertion of TAMs, and their correlation with tumor development, metastasis and prognosis. Furthermore, we present the current research progress on modulating the effects of TAMs with chemokine antagonists and discuss the prospects and potential challenges of using chemokine antagonists as therapeutic tools for cancer treatment. The TAMs targeting by chemokine receptor antagonists in combination with chemotherapy drugs, immune checkpoint inhibitors or radiotherapy appears to be a promising approach.