Language
English
Publication Date
10-5-2026
Journal
Cancer Immunology Research
DOI
10.1158/2326-6066.CIR-25-1639
PMID
42536056
PMCID
PMC13557767
PubMedCentral® Posted Date
9-10-2026
PubMedCentral® Full Text Version
Author MSS
Abstract
Immune checkpoint inhibitor (ICI) therapy is often associated with immune-related adverse events including inflammatory arthritis (IA). However, the mechanisms underlying ICI-mediated IA (ICI-IA), especially its recurrence, are not well understood. In this study, we sought to elucidate mechanisms of recurrent ICI-IA by analyzing longitudinal synovial fluid (SF) samples from patients with ICI-IA. SF samples were collected from six patients with ICI-IA at the first and second occurrences of ICI-IA and analyzed with single-cell RNA sequencing (n = 3), single-cell T-cell receptor sequencing (n = 3), single-cell B-cell receptor sequencing (n = 3), and flow cytometry (n = 6). SF samples from cancer-naïve patients with osteoarthritis (n = 6) were used as negative controls. Analysis revealed that effector CD8+ T cells and PD-1hiCXCL13hi CD4+ T cells were enriched in the SF of patients with ICI-IA. A total of 93% and 50% of the top 10 expanded clones of effector CD8+ T cells and PD-1hiCXCL13hi CD4+ T cells, respectively, were shared between the first and second ICI-IA flares. These top clones were characterized by the production of pro-inflammatory type 1 cytokines including IFNγ, TNFα, and IL21, especially in the second flare, suggesting immune memory responses to cognate antigen. Cell-cell communication analysis suggested that effector CD8+ T cells and PD-1hiCXCL13hi CD4+ T cells interacted with each other and with myeloid cells and B cells through chemokines (CXCL9/10/11/13 and CCL3) and cytokines (macrophage inhibitory factor and IL2/7/15/21). Overall, longitudinal SF analysis from patients with ICI-IA revealed the expansion of effector CD8+ T cells and PD-1hiCXCL13hi CD4+ T cells with type 1 cytokine signatures that potentially contribute to the development or recurrence of ICI-IA.
Keywords
Humans, Immune Checkpoint Inhibitors, Female, Arthritis, CD8-Positive T-Lymphocytes, Synovial Fluid, Male, CD4-Positive T-Lymphocytes, Aged, Recurrence, Middle Aged, Cytokines
Published Open-Access
yes
Recommended Citation
Keam, Synat; Li, Yuanteng Jeff; Chu, Yanshuo; et al., "Immune Hallmarks of Recurrent Immune Checkpoint Inhibitor-Mediated Inflammatory Arthritis" (2026). Faculty, Staff and Students Publications. 8742.
https://digitalcommons.library.tmc.edu/baylor_docs/8742