Related Experiment Video

Updated: May 17, 2026

Monitoring PD-1-Blocking Antibodies Bound to T Cells Derived from a Drop of Peripheral Blood
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
PubMed

Immune checkpoint blockade-induced immune-related adverse events (irAE) hamper the application of this revolutionary antitumor therapeutic strategy. In this study, we explored the mechanisms driving irAEs by profiling the immune ecosystem of major irAE-affected organs at the single-cell scale. The analysis identified 3 populations of cytotoxic T lymphocytes that mediate antitumor immunity (CTL1) or that induce irAE in the gut (CTLirAE-I) or in multiple other organs (CTLirAE-II). Interleukin-JAK1 signaling was specifically activated in the CTLirAE-II population upon PD-1 blockade. Targeting JAK1 remarkably relieved the irAEs in the heart and lung without compromising antitumor efficacy. Tracking T-cell receptor sequence and transcriptome showed that CTLirAE-II and CTL1 populations originated from lymph node progenitor cells, whereas the CTLirAE-I population was derived from tissue-resident memory T cells. Moreover, irAEs could be monitored by assessing the CTLirAE-II population in circulation. In conclusion, this study elucidates the landscape of cellular changes in irAEs across multiple organs after immunotherapy and proposes strategies for relieving irAE symptoms and facilitating diagnosis.

More Related Videos

Identifying PD-1/PD-L1 Inhibitors with Surface Plasmon Resonance Technology07:04

Identifying PD-1/PD-L1 Inhibitors with Surface Plasmon Resonance Technology

Published on: May 2, 2025

Tailoring In Vivo Cytotoxicity Assays to Study Immunodominance in Tumor-specific CD8+ T Cell Responses10:13

Tailoring In Vivo Cytotoxicity Assays to Study Immunodominance in Tumor-specific CD8+ T Cell Responses

Published on: May 6, 2019

Related Concept Videos

T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Cell-mediated Immune Responses01:40

Cell-mediated Immune Responses

Overview
Drug Toxicity: Allergic Reactions01:30

Drug Toxicity: Allergic Reactions

Drug-related allergies are immune-mediated responses triggered by the administration of pharmacological agents. These hypersensitivity reactions are classified based on the immune mechanisms involved. The four primary types—Type I, II, III, and IV—are mediated by different immunological pathways and exhibit distinct clinical manifestations.Type I Hypersensitivity/ IgE-Mediated Reactions: Immunoglobulin E (IgE) immediately mediates Type I hypersensitivity reactions. Upon initial exposure to a...
Inflammatory Bowel Disease III: Crohn's Disease01:25

Inflammatory Bowel Disease III: Crohn's Disease

Crohn’s disease is a chronic, relapsing form of inflammatory bowel disease characterized by segmental, transmural inflammation that can affect any part of the gastrointestinal tract. Its pathogenesis arises from a combination of genetic susceptibility, environmental exposures, epithelial barrier dysfunction, and immune dysregulation. Together, these factors lead to an exaggerated immune response against components of the gut microbiome.Genetic and Environmental InfluencesMultiple genetic...
Inflammatory Response01:28

Inflammatory Response

An inflammatory response is a localized, nonspecific immune reaction that occurs when a tissue is injured. It is characterized by redness, swelling, heat, and pain, which are commonly called the cardinal signs and symptoms of inflammation. Inflammation can sometimes result in a loss of function.
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...