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Review
. 2025 Aug;46(8):562-572.
doi: 10.1016/j.it.2025.06.003. Epub 2025 Jul 11.

GZMK+CD8+ T cells: multifaceted roles beyond cytotoxicity

Cui-Lian Guo  1 , Chong-Shu Wang  1 , Xiang-Hong Wang  1 , Di Yu  2 , Zheng Liu  3
Affiliations
Review

GZMK+CD8+ T cells: multifaceted roles beyond cytotoxicity

Cui-Lian Guo et al. Trends Immunol. 2025 Aug.

Abstract

CD8+ T cells, traditionally recognized for their cytotoxic role in eliminating infections and malignancies, are now known to exhibit significant functional heterogeneity, as revealed by single-cell genomics. Among these, granzyme-K-expressing (GZMK+) CD8+ T cells represent a distinct subset characterized by low cytotoxicity but heightened proinflammatory activity, by contrast with their granzyme-B-expressing (GZMB+) counterparts with high cytotoxicity. GZMK+CD8+ T cells are often more abundant in inflammatory diseases, cancer, and age-related inflammation (inflammaging). These cells interact with stromal cells, activate the complement cascade, and perpetuate inflammation, highlighting their emerging therapeutic significance. We review the latest advances in the biology and pathological roles of GZMK+CD8+ T cells, and discuss the potential of targeting their dysregulated activities to treat chronic inflammation and malignancies.

Keywords: CD8(+) T cells; cancer; granzyme B; granzyme K; inflammation.

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Conflict of interest statement

Declaration of interests The authors have no interests to declare.