Revisiting TAM polarization: beyond M1- and M2-type TAM toward clinical precision in macrophage-targeted therapy

Tumor-associated macrophages (TAMs) are key regulators of the tumor microenvironment (TME), significantly influencing cancer progression and therapeutic responses. TAMs polarize into M1 or M2 phenotypes, exerting distinct functional roles. M1-type macrophages promote inflammation and tumor cell dest...

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Main Authors: Qingqing Wang, Wenxue Ma
Format: Article
Language:English
Published: Elsevier 2025-09-01
Series:Experimental and Molecular Pathology
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Online Access:http://www.sciencedirect.com/science/article/pii/S0014480025000322
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author Qingqing Wang
Wenxue Ma
author_facet Qingqing Wang
Wenxue Ma
author_sort Qingqing Wang
collection DOAJ
description Tumor-associated macrophages (TAMs) are key regulators of the tumor microenvironment (TME), significantly influencing cancer progression and therapeutic responses. TAMs polarize into M1 or M2 phenotypes, exerting distinct functional roles. M1-type macrophages promote inflammation and tumor cell destruction, whereas M2-type macrophages facilitate immune suppression, angiogenesis, and metastasis. However, inconsistencies and mischaracterizations in the literature regarding TAM classification have led to confusion in the field, potentially impeding the development of effective macrophage-targeted immunotherapies. This commentary highlights the need for clear and standardized nomenclature, clarifies the functional distinctions between M1- and M2- type TAMs, and explores the signaling pathways and environmental factors driving their polarization. We also discuss emerging TAM subtypes and the therapeutic significance of accurate classification, including macrophage reprogramming strategies. Standardizing terminology and addressing misconceptions will be critical to advancing macrophage-based immunotherapies and improving clinical outcomes in cancer treatment.
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spelling doaj-art-23f79db92fd74cf1aa5b39645bc6a9812025-08-20T03:50:31ZengElsevierExperimental and Molecular Pathology1096-09452025-09-0114310498210.1016/j.yexmp.2025.104982Revisiting TAM polarization: beyond M1- and M2-type TAM toward clinical precision in macrophage-targeted therapyQingqing Wang0Wenxue Ma1Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, ChinaDepartment of Medicine, Sanford Stem Cell Institute, Moores Cancer Center, University of California San Diego, La Jolla, CA 92093, USA; Corresponding author.Tumor-associated macrophages (TAMs) are key regulators of the tumor microenvironment (TME), significantly influencing cancer progression and therapeutic responses. TAMs polarize into M1 or M2 phenotypes, exerting distinct functional roles. M1-type macrophages promote inflammation and tumor cell destruction, whereas M2-type macrophages facilitate immune suppression, angiogenesis, and metastasis. However, inconsistencies and mischaracterizations in the literature regarding TAM classification have led to confusion in the field, potentially impeding the development of effective macrophage-targeted immunotherapies. This commentary highlights the need for clear and standardized nomenclature, clarifies the functional distinctions between M1- and M2- type TAMs, and explores the signaling pathways and environmental factors driving their polarization. We also discuss emerging TAM subtypes and the therapeutic significance of accurate classification, including macrophage reprogramming strategies. Standardizing terminology and addressing misconceptions will be critical to advancing macrophage-based immunotherapies and improving clinical outcomes in cancer treatment.http://www.sciencedirect.com/science/article/pii/S0014480025000322Tumor-associated macrophages (TAMs)M1 and M2 macrophagesMacrophage polarizationM2 macrophage subtypesTumor microenvironment (TME)Cancer immunotherapy
spellingShingle Qingqing Wang
Wenxue Ma
Revisiting TAM polarization: beyond M1- and M2-type TAM toward clinical precision in macrophage-targeted therapy
Experimental and Molecular Pathology
Tumor-associated macrophages (TAMs)
M1 and M2 macrophages
Macrophage polarization
M2 macrophage subtypes
Tumor microenvironment (TME)
Cancer immunotherapy
title Revisiting TAM polarization: beyond M1- and M2-type TAM toward clinical precision in macrophage-targeted therapy
title_full Revisiting TAM polarization: beyond M1- and M2-type TAM toward clinical precision in macrophage-targeted therapy
title_fullStr Revisiting TAM polarization: beyond M1- and M2-type TAM toward clinical precision in macrophage-targeted therapy
title_full_unstemmed Revisiting TAM polarization: beyond M1- and M2-type TAM toward clinical precision in macrophage-targeted therapy
title_short Revisiting TAM polarization: beyond M1- and M2-type TAM toward clinical precision in macrophage-targeted therapy
title_sort revisiting tam polarization beyond m1 and m2 type tam toward clinical precision in macrophage targeted therapy
topic Tumor-associated macrophages (TAMs)
M1 and M2 macrophages
Macrophage polarization
M2 macrophage subtypes
Tumor microenvironment (TME)
Cancer immunotherapy
url http://www.sciencedirect.com/science/article/pii/S0014480025000322
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