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Data · dataset · 2025

Pathogenic CD137+ IL-17+ atypical Treg is a unique feature of immune checkpoint inhibitor-induced inflammatory arthritis and is abrogated by IL-6R blockade

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Immune checkpoint inhibitor-induced inflammatory arthritis (ICI-IA) significantly impairs cancer therapy and patient quality of life, yet its pathogenic mechanisms remain unclear.

Description

Through integrated single-cell multi-omics analysis of paired peripheral blood, synovial fluid, and tumor samples from longitudinal ICI-IA cohorts and matched controls, we identified a unique regulatory T-cell (Treg) population co-expressing CD137 and IL-6R (AtpTreg).

These cells exhibited reduced immunosuppressive capacity while aberrantly producing high level of IL-17 and promoting proinflammatory responses of synoviocytes. AtpTreg exhibits shared clonotypes and phenotypes across tissue compartments. Notably, AtpTreg frequency correlates with increased arthritis severity yet paradoxically associates with improved overall survival.

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Anti-IL6R therapy reduced AtpTreg levels, corresponding with improved arthritis outcomes and quality of life, without compromising anti-tumor immunity. Our findings define a pathogenic Treg subset in ICI-IA and validate IL-6R blockade as a mechanism-based therapeutic strategy, bridging mechanistic discovery to clinical translation.

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Inferred from text
Cancer 75% · Immunology 69% · Longitudinal study 65%
Provenance · 1 source records, 14 field assertions
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ScienceDB10.57760/sciencedb.2930011 d agoJSON v1
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