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Updated: Jul 2, 2026

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Generation of Human Chimeric Antigen Receptor Regulatory T Cells
Published on: January 3, 2025
Checkpoint inhibitors create rogue regulatory T cells.
The Journal of Clinical Investigation
|July 1, 2026
Summary
Researchers discovered atypical regulatory T cells (AtpTregs) linked to immune checkpoint inhibitor-induced inflammatory arthritis (ICI-IA). Targeting these cells with anti-IL6R therapy may treat ICI-IA while preserving anti-tumor immunity.
Area of Science:
- Immunology
- Oncology
- Rheumatology
Background:
- Immune checkpoint inhibitors (ICIs) treat cancer but can cause immune-related adverse events (irAEs).
- Immune checkpoint inhibitor-induced inflammatory arthritis (ICI-IA) is a significant irAE.
- Regulatory T cells (Tregs) normally suppress immune responses.
Purpose of the Study:
- To identify immune cells involved in ICI-IA.
- To investigate the function and therapeutic potential of these cells.
Main Methods:
- Identification and characterization of a novel Treg subset (AtpTregs) in patients with ICI-IA.
- Functional assays to assess AtpTreg suppressive capacity and phenotype.
- Analysis of the association between AtpTregs, arthritis severity, and cancer outcomes.
- Evaluation of anti-IL6R therapy (tocilizumab) in a small cohort of patients with ICI-IA.
Main Results:
- A subset of Tregs, termed atypical Tregs (AtpTregs), coexpressing CD137 and IL-6 receptor (IL6R), were enriched in patients with ICI-IA.
- AtpTregs showed reduced suppressive function and a proinflammatory phenotype.
- Higher AtpTreg levels correlated with more severe arthritis but also improved cancer outcomes.
- Tocilizumab treatment reduced AtpTreg abundance, alleviated arthritis, and maintained antitumor immunity.
Conclusions:
- AtpTregs are a key cellular player in ICI-IA pathogenesis.
- Targeting IL-6 receptor with therapies like tocilizumab may effectively manage ICI-IA.
- Anti-IL6R therapy holds potential for treating ICI-IA and other irAEs involving AtpTregs, while preserving anti-tumor effects.
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