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Updated: May 17, 2026
06:07
Monitoring PD-1-Blocking Antibodies Bound to T Cells Derived from a Drop of Peripheral Blood
Published on: February 5, 2020
Distinct Inflammatory Cytotoxic T Lymphocyte Populations Mediate PD-1 Blockade-Induced Immune-Related Adverse Events
Xiaowei Liu1,2, Jinen Song1, Fengli Zuo1
1Institute for Breast Health Medicine, State Key Laboratory of Biotherapy, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, China.
Cancer Research
|May 15, 2026
Summary
Immune checkpoint blockade can cause immune-related adverse events (irAEs). Targeting JAK1 signaling in specific T cell populations reduced irAEs in organs like the heart and lung without affecting anti-tumor immunity.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- Immune checkpoint blockade (ICB) is a revolutionary cancer therapy.
- Immune-related adverse events (irAEs) limit the clinical application of ICB.
- Understanding the cellular mechanisms of irAEs is crucial for improving cancer treatment.
Purpose of the Study:
- To investigate the cellular and molecular mechanisms underlying ICB-induced irAEs.
- To identify distinct T cell populations involved in anti-tumor immunity and irAEs.
- To explore therapeutic strategies for mitigating irAEs.
Main Methods:
- Single-cell profiling of immune cells in irAE-affected organs.
- Analysis of T cell receptor (TCR) sequences and transcriptomes.
- Pharmacological targeting of specific signaling pathways (JAK1).
Main Results:
- Identified three cytotoxic T lymphocyte (CTL) populations: CTL1 (anti-tumor), CTLirAE-I (gut irAEs), and CTLirAE-II (multi-organ irAEs).
- Interleukin-JAK1 signaling was specifically activated in CTLirAE-II cells upon PD-1 blockade.
- Targeting JAK1 ameliorated irAEs in the heart and lung without compromising anti-tumor efficacy.
- CTLirAE-II and CTL1 cells originate from lymph node progenitors, while CTLirAE-I cells derive from tissue-resident memory T cells.
- Circulating CTLirAE-II levels can serve as a biomarker for monitoring irAEs.
Conclusions:
- Elucidated the cellular landscape of irAEs across multiple organs.
- Demonstrated the therapeutic potential of targeting JAK1 signaling to manage irAEs.
- Proposed strategies for irAE symptom relief and diagnostic monitoring.
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