Metabolic and epigenetic plasticity of tumor-associated macrophages shapes immunosuppressive outputs and immune checkpoint response.

Authors

Jinghao Pan, Boyang Li, Lucy Yue Lau, Zehao Hong, Yi Chen

Published in

Biochimica et biophysica acta. Reviews on cancer. Pages 189702. Sep 08, 2026. Epub Sep 08, 2026.

Abstract

Immune checkpoint blockade (ICB) has transformed cancer therapy, but durable responses are frequently limited by tumor microenvironment-driven resistance. Tumor-associated macrophages (TAMs) are central mediators of this process because they sense metabolic stress and convert it into immunosuppressive programs that restrict antigen presentation, effector T cell entry, and cytotoxic function. This review conceptualizes the tumor microenvironment as a metabolic ecosystem shaped by hypoxia, lactate accumulation, acidosis, nutrient competition, lipid-rich niches, and amino-acid scarcity. We propose a context-dependent state-transition model in which these pressures are decoded by interconnected nutrient- and stress-sensing pathways, integrated through mitochondrial bioenergetic and redox adaptation, and translated by metabolite-dependent chromatin remodeling into persistent TAM functional programs that constrain the depth and durability of ICB responses. We further link glucose, lipid, and amino-acid metabolic circuitry to checkpoint resistance and propose therapeutic leverage tiers and biomarker layers for TAM metabolic reprogramming combined with ICB. This framework highlights actionable routes to overcome myeloid-driven immune resistance.

PMID:
42710817
Bibliographic data and abstract were imported from PubMed on 09 Sep 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.