M2 Macrophage Polarization: Signaling Pathways, Metabolic Reprogramming, and Targeting Strategies in Cancer Therapy

Abstract

In the microenvironment of the tumor, there are two subpopulations of tumor associated macrophages (TAMs) with opposite functions: proinflammatory M1 macrophages and immunosuppressive M2 macrophages. Among them, M2-like macrophages' primary function in TME is inhibiting immune response and promoting tumor progression. In order to combat the immunosuppressive effect of M2-like TAMs, this article examines the variables linked to TAM polarization as well as possible tactics for directing TAM repolarization to the M1 pro-inflammatory phenotype for cancer treatment. This article systematically expounds how to intervene tumor progression by targeting the polarization of M2 macrophages, including: 1) An outline of M2 macrophages' function in the TME; 2) The signaling pathways related to TAM polarization (such as STAT family signaling pathway, PI3K/Akt signaling pathway), the reprogramming of cellular metabolic pathways, and the involvement of tumor derived exosomal ncRNA were introduced; 3) A variety of methods to target TAM's orientation to the pro-inflammatory M1 phenotype are discussed, such as signaling pathway inhibition, metabolic intervention, exosomes and other targeting strategies. Therefore, targeting M2 macrophage polarization is an effective strategy to reverse tumor progression, providing a new perspective for cancer therapy.