Macrophages in tumors with downregulated MHC-I expression: emerging therapeutic opportunities and translational challenges.

Authors

Adrianna Piatakova, Michal Smahel

Published in

Clinical and experimental immunology. Aug 11, 2026. Epub Aug 11, 2026.

Abstract

Tumor-associated macrophages (TAMs) are the dominant component of the tumor microenvironment (TME) and exhibit remarkable phenotypic plasticity and heterogeneity that extends beyond the classical M1/M2 polarization, as revealed by single-cell transcriptomics across multiple cancer types. Downregulation of major histocompatibility complex class I (MHC-I) on tumor cells is a common immune evasion strategy that profoundly shapes TAM composition and function. Conversely, TAMs reciprocally modulate tumor MHC-I expression. This review provides an overview of the verified and hypothetical mechanisms of bidirectional regulatory interactions between MHC-I on tumor cells and TAMs. Since these interactions likely differ between tumors with reversible and irreversible MHC-I downregulation, their potential significance in tumor immunotherapy should be assessed separately for each MHC-I reduction mechanism.

PMID:
42579859
Bibliographic data and abstract were imported from PubMed on 12 Aug 2026.

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