The role of macrophage in regulating tumour microenvironment and the strategies for reprogramming tumour-associated macrophages in antitumour therapy

Abstract

Tumour-associated macrophages (TAMs) that present abundantly in the tumour microenvironment (TME) exhibit a protumour property, such as promoting genetic instability, tumour metastasis and immunosuppression. Macrophage-targeted therapeutic approaches hence have been applied and shown their significances in the process of tumour immune treatment, including blocking TAM recruitment, depleting or transforming TAMs that already exist in the tumour site. Here, we summarized the functional regulation of TAMs in the respects of hypoxia environment, metabolism in the tumour microenvironment and the transcription factors involved. We reviewed the strategies for transforming TAMs, including immune stimuli targeting TAMs, inhibitors against TAMs, pathogen or irradiation stimulation on TAMs, and the application of natural compounds in TAMs. Furthermore, we also discussed the macrophage-targeted therapies in the clinical studies. Taken together, this review tries to shed light on the TAM regulation and the main strategies of TAM reprogramming for an enhanced immune surveillance.

Keywords: Immunotherapy; TAM transformation; TME; Tumour.