Tumor-Associated Macrophage Subsets: Shaping Polarization and Targeting

Abstract

The tumor microenvironment (TME) is a critical regulator of tumor growth, progression, and metastasis. Among the innate immune cells recruited to the tumor site, macrophages are the most abundant cell population and are present at all stages of tumor progression. They undergo M1/M2 polarization in response to signals derived from TME. M1 macrophages suppress tumor growth, while their M2 counterparts exert pro-tumoral effects by promoting tumor growth, angiogenesis, metastasis, and resistance to current therapies. Several subsets of the M2 phenotype have been observed, often denoted as M2a, M2b, M2c, and M2d. These are induced by different stimuli and differ in phenotypes as well as functions. In this review, we discuss the key features of each M2 subset, their implications in cancers, and highlight the strategies that are being developed to harness TAMs for cancer treatment.

Estrogen contributes to sex differences in M2a macrophages during multi‐walled carbon nanotube‐induced respiratory inflammation

“…However, historically, macrophages have been generally categorized using “classically” activated M1 or “alternatively” activated M2 nomenclature, 20 which corresponds to traditional Th1/Th2 immune response classifications 21 . M2 macrophages can further be classified into subtypes including the M2a phenotype; this phenotype is induced by IL‐4/IL‐13 signaling and displays enhanced endocytic activity, promotes cellular proliferation and tissue remodeling, but also produces type 2 inflammatory signals 22 . M2a macrophages are protective against helminth and fungal infection, 23–26 but can also sustain type 2 inflammation in an inappropriate manner.…”

Anti‐inflammatory mechanisms in cancer research: Characterization of a distinctM2‐like macrophage model derived from theTHP‐1 cell line

“…This provides the basis for investigating mechanisms mediated by anti‐inflammatory macrophages in vitro 38 . Macrophages can be divided into several subsets from M2a‐d 59 . These subsets have been investigated in association with the development of different cancers, and their gene expression profiles are overlapping.…”

“…This provides the basis for investigating mechanisms mediated by anti-inflammatory macrophages in vitro. 38 Macrophages can be divided into several subsets from M2a-d. 59 These subsets have been investigated in association with the T A B L E 5 scRNA-Seq marker expression in peripheral blood monocytes (N = 2099) versus primary human colon cancer tissue TAMs (N = 103).…”

In Situ Reprogramming of Immune Cells Using Synthetic Nanomaterials

“…They are one of the most abundant cell types in diverse solid tumors, in some cases contributing up to 50% of the tumor mass. [ 61–63 ] Typically, macrophages can be polarized into M1‐like and M2‐like phenotypes. M1‐like macrophages produce proinflammatory cytokines, mediate phagocytosis of pathogens, and initiate immune responses.…”