Mitochondrial regulation of tumor-associated macrophage function
10 affiliations
- 1Department of Traditional Chinese Internal Medicine, School of Traditional Chinese Medicine, Southern Medical University
- 2Department of Rheumatology and Immunology, Nanfang Hospital, Southern Medical University
- 3The First School of Clinical Medicine, Southern Medical University
- 4The Second Affiliated Hospital of Guilin Medical University
- 5School of Basic Medical Sciences, Guangzhou University of Chinese Medicine
- 6Department of Nephrology and Rheumatology, The Affiliated Traditional Chinese Medicine Hospital, Guangzhou Medical University
- 7Department of Radiology, the Second Affiliated Hospital, University of South China
- 8Department of Pharmacy, The Seventh Affiliated Hospital, Southern Medical University
- 9Department of Rheumatology and Clinical Immunology, The First Affiliated Hospital of Guangzhou Medical University
- 10Institute for Clinical Medical Research, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University
Abstract
Tumor-associated macrophages (TAMs) adapt to hypoxia, nutrient competition, lipid accumulation, and anticancer treatment. Mitochondria contribute to this adaptation through energy metabolism, redox signaling, mitochondrial DNA (mtDNA) sensing, and metabolite-dependent regulation of gene expression. This Review examines mitochondrial dynamics, mitophagy, proteostasis, respiratory remodeling, and lipid-droplet interactions, distinguishing direct TAM evidence from findings in other experimental systems. Tumor studies link these processes to IL-12 and IL-10 production, interferon responses, antigen presentation, and lymphocyte recruitment, with effects that vary by pathway and macrophage state. These findings do not establish a single optimal level of mitochondrial quality control. We discuss how macrophage lineage, spatial niche, and treatment exposure may influence the response to mitochondrial interventions. Therapeutic development will require causal validation in defined TAM populations, selective delivery, and measurements of immune function alongside mitochondrial changes. Evidence in human TAMs and direct studies of organelle contacts remain limited. Somatic mtDNA variation is considered separately from altered gene expression and DNA release, with lineage-tracing evidence distinguished from functional causation.
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BibTeX
@article{xu2026mitochondrial,
title = {{Mitochondrial regulation of tumor-associated macrophage function}},
author = {Jiabao Xu and Yangtao Liu and Hongjie Zhang and Zhao Yuan and Sheng Yu and Xiaodong Wang and Hanbin Liu and Fei Zhong and Hui Zhang and Han Xiong and Xiaoling Chen and Qingqing Zhang and Jiani Liu and Li Cai and Qizhen Huang and Heying Yue and Liang Huang and Ning Zhu and Yi Yuan and Meng Li and Chengkai Wu},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1971517},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1971517/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Mitochondrial regulation of tumor-associated macrophage function
AU - Jiabao Xu
AU - Yangtao Liu
AU - Hongjie Zhang
AU - Zhao Yuan
AU - Sheng Yu
AU - Xiaodong Wang
AU - Hanbin Liu
AU - Fei Zhong
AU - Hui Zhang
AU - Han Xiong
AU - Xiaoling Chen
AU - Qingqing Zhang
AU - Jiani Liu
AU - Li Cai
AU - Qizhen Huang
AU - Heying Yue
AU - Liang Huang
AU - Ning Zhu
AU - Yi Yuan
AU - Meng Li
AU - Chengkai Wu
PY - 2026
DA - 2026/10/07
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1971517
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1971517/full
AB - Tumor-associated macrophages (TAMs) adapt to hypoxia, nutrient competition, lipid accumulation, and anticancer treatment. Mitochondria contribute to this adaptation through energy metabolism, redox signaling, mitochondrial DNA (mtDNA) sensing, and metabolite-dependent regulation of gene expression. This Review examines mitochondrial dynamics, mitophagy, proteostasis, respiratory remodeling, and lipid-droplet interactions, distinguishing direct TAM evidence from findings in other experimental systems. Tumor studies link these processes to IL-12 and IL-10 production, interferon responses, antigen presentation, and lymphocyte recruitment, with effects that vary by pathway and macrophage state. These findings do not establish a single optimal level of mitochondrial quality control. We discuss how macrophage lineage, spatial niche, and treatment exposure may influence the response to mitochondrial interventions. Therapeutic development will require causal validation in defined TAM populations, selective delivery, and measurements of immune function alongside mitochondrial changes. Evidence in human TAMs and direct studies of organelle contacts remain limited. Somatic mtDNA variation is considered separately from altered gene expression and DNA release, with lineage-tracing evidence distinguished from functional causation.
SN - 1664-3224
ER -