Roles of Tumor-Associated Macrophages in Tumor Environment and Strategies for Targeting Therapy

Abstract

Tumor-associated macrophages (TAMs) constitute a significant component of the tumor microenvironment. This work reviewed the latest progress in comprehending the function of TAMs and their strategies for cancer therapy. TAMs are highly heterogeneous and plastic and exhibit different functional phenotypes in response to different signal stimuli. The emergence of single-cell technologies allows us to revisit their diversity in cancer. When their pro-inflammatory function is activated, antitumor TAMs support and activate adaptive immune cells to eliminate cancer cells through T cell-mediated killing. In the context of cancer, anti-inflammatory TAMs play a variety of pro-tumor functions, such as releasing cytokines to promote the recruitment of bone marrow cells, promoting tumor angiogenesis, and inhibiting cytotoxic T cell function. The plasticity of TAMs makes them a potential tumor therapeutic target, so finally, we updated strategies for targeting TAMs and the TAM-targeting agents currently being evaluated in clinical trials.

Keywords

tumor-associated macrophages - inflammation - cancer immunotherapy - tumor microenvironment

Supporting Information

Detailed information for representative clinical trials of TAM-targeting agents and strategies for anticancer therapy ([Table S1], available in the online version), and chemical structural and corresponding targets of small-molecule compounds mentioned in the text (BLZ945, pexidartinib, 3D-185, PF-04136309, maraviroc, BMS 813160, cediranib, rintatolimod) ([Table S2], available in the online version); as well as TAMs targeting-related studies including the significant progress, advantages, and limitations ([Table S3], available in the online version), are included in the Supporting Information ([Table S1]–[S3], available in the online version).

^# These authors contributed to this work equally.

Publication History

Received: 10 September 2023

Accepted: 17 November 2023

Article published online:
13 December 2023

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