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Leveraging macrophage plasticity for precision-targeted tumor immunotherapy.
Shu-Jin Li1, Xiao-He Wang1, Ling-Rui Li1
1State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China.
Biochimica Et Biophysica Acta. Molecular Basis of Disease
|January 31, 2026
Summary
Tumor-associated macrophages (TAMs) within the tumor microenvironment (TME) hinder immunotherapy efficacy. Targeting TAMs through novel strategies like reprogramming offers a promising approach to enhance cancer treatment outcomes.
Area of Science:
- Oncology
- Immunology
- Cancer Biology
Background:
- Immunotherapy shows promise but faces suboptimal clinical efficacy.
- The tumor microenvironment (TME), particularly tumor-associated macrophages (TAMs), significantly impacts immunotherapy response, prognosis, and resistance.
- The traditional M1/M2 macrophage classification is insufficient to describe TAM complexity.
Purpose of the Study:
- To critically review TAM heterogeneity beyond the M1/M2 paradigm.
- To explore therapeutic strategies targeting TAMs.
- To assess the synergistic potential of TAM-targeted therapies with existing immunotherapies.
Main Methods:
- Comprehensive literature review of TAM heterogeneity and function.
- Systematic examination of therapeutic strategies targeting TAMs: recruitment inhibition, depletion, and phenotypic reprogramming.
- Analysis of synergistic potential with current immunotherapies.
Main Results:
- TAMs exhibit significant heterogeneity and plasticity, defying simple M1/M2 categorization.
- Targeting TAMs via recruitment inhibition, depletion, or reprogramming presents viable therapeutic avenues.
- Combining TAM-targeting strategies with immunotherapy holds potential to overcome treatment resistance.
Conclusions:
- Understanding TAM heterogeneity is crucial for improving immunotherapy.
- Multifaceted TAM-targeting strategies can enhance cancer treatment efficacy.
- Developing combination therapies involving TAM modulation is key to overcoming current limitations in cancer immunotherapy.
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