Macrophages: Traffic centers in the tumor immune microenvironment

Abstract

The tumor microenvironment (TME) has emerged as a prominent focus of cancer research in recent years, with various drugs in this field, including programmed cell death receptor 1 (PD-1) antibodies and cytotoxic T lymphocyte antigen 4 (CTLA-4) antibodies, now included in first-line therapeutic guidelines for cancer. Although macrophages are not as effective as T-lymphocytes in directly killing tumors, they serve as critical mediators in the TME due to their indirect roles in promoting blood vessel formation, facilitating antigen presentation and influencing tumor cell metabolism to affect their infiltration. Macrophages are governed by complex regulatory networks, both independently and as a part of the TME. Extensive research has led to the development of a comprehensive and detailed understanding of these networks and the molecular mechanisms driving macrophage activity. The interactions between macrophages and the TME significantly impact tumor initiation and progression, making macrophages a promising target for cancer therapy. In this review, we discuss recent findings on the factors underlying macrophage polarization in the TME, the critical role of macrophages within the TME, key transcriptional regulators of macrophages, and emerging strategies for targeting macrophages in cancer therapy.