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TREM2⁺ tumor-associated macrophages in cancer: Context-dependent biology, biomarkers, and precision immunotherapy

Critical Reviews in Oncology/Hematology·September 15Open Access
HematologyLimited evidenceCancerSolid TumorsNarrative ReviewImmunotherapyMacrophage ReprogrammingMonoclonal AntibodyMixed

Summary

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What was studied

This review synthesizes current understanding of TREM2⁺ tumor-associated macrophages (TAMs) across multiple solid tumors, covering their signaling, immunometabolic roles, immune evasion mechanisms, clinical associations, and emerging therapeutic strategies targeting this myeloid population.

Key findings

TREM2⁺ TAMs are linked to metabolic adaptation, immune evasion, and impaired antitumor immunity, but their biological functions vary substantially by tumor type, tissue niche, macrophage ontogeny, and microenvironmental context; the review proposes a context-dependent framework to guide biomarker development and precision immunotherapy.

Study limitations

As a narrative review, it does not pool original data or provide quantitative effect estimates; conflicting findings across tumor types are acknowledged but not resolved by meta-analysis; translational gaps between preclinical models and human disease remain.

Clinical implications

TREM2⁺ macrophage abundance and spatial distribution may serve as candidate biomarkers for immunotherapy response; clinicians should be aware that targeting this population (via antibody-based approaches, macrophage reprogramming, or combination immunotherapy) is still in early translational stages with unresolved safety considerations.

Caveats

  • Conflicting clinical associations of TREM2⁺ TAMs with outcomes across tumor types reflect genuine biological heterogeneity, not just methodological differences
  • Therapeutic strategies discussed (antibody-based targeting, macrophage reprogramming) are in early translational or preclinical stages; no approved therapies directly targeting TREM2 in cancer are established
  • TREM2⁺ TAM biology is context-dependent and findings should not be generalized across tumor types without accounting for tissue niche and macrophage ontogeny

Related Questions

Explore related topics

What therapeutic antibodies are being developed to target TREM2+ tumor-associated macrophages?How does TREM2 expression in the tumor microenvironment predict response to checkpoint immunotherapy?What is the role of macrophage ontogeny and tissue context in shaping TREM2+ TAM function across solid tumors?

Publication Details

Year
2026
Journal
Critical Reviews in Oncology/Hematology
Source
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