Crosstalk between tumor-associated macrophages and the B7/CD28 family in immune checkpoint inhibitor-induced immunotherapy.

The tumor microenvironment (TME) is a complex ecosystem containing various cells and secreted molecules that play critical roles in the progression of tumorigenesis. In recent years, antitumor strategies aimed at reshaping the TME have attracted much attention. Tumor-associated macrophages (TAMs) are the most abundant immune cells infiltrating the TME, contributing more than 50% of the tumor mass. In a variety of cancers, TAMs participate in the processes of tumor formation, migration, and invasion and are significantly related to a poor prognosis. Furthermore, TAMs play crucial roles in the regulation of the TME, chemoresistance, and immunotherapy resistance, and are potential targets in tumor therapy. TAMs are supposed to be carriers of ligands of immune checkpoint inhibitors (ICIs). Therefore, it is expected that TAMs can regulate T cell immune function through providing costimulatory/coinhibitory signals and may significantly influence the immune response related to ICIs. B7/CD28 family members are the best studied immune checkpoint receptors and ligands. Several studies have demonstrated that these B7/CD28 family members are highly expressed on TAMs, eliminating the inhibitory signal of T cell activation. However, the role of TAMs and B7/CD28 family members in ICI-induced immunotherapy is complicated and need to be illustrated. This study aims to review the crosstalk between TAMs and the B7/CD28 family, highlight the role of TAM-mediated tumor immune escape in ICI immunotherapy, explore the application prospects of TAMs in reversing ICI resistance.