ORIGINAL RESEARCH article
Front. Oncol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1628790
This article is part of the Research TopicImmunomodulatory Effects of Regulatory T Cells (Treg) and Treg-Derived Extracellular VesiclesView all articles
Phenotypes of synovial fluid Treg cells in checkpoint blockade-related inflammatory arthritis
Provisionally accepted
Heyu He1,2
Ning Zhou3Kaidi Wu1Junhong Lin1Shaowei Zhou1Yuntao Gu1
Xinjia Wang4,5Weidong Wang4Lichuan Mo1
Chuanzhu Lv6*- 1The Second Affiliated Hospital of Hainan Medical University, Haikou, China
- 2The Emergency and Trauma College, Hainan Medical University, Haikou, China
- 3Central People's Hospital of Zhanjiang, Zhanjiang, China
- 4Cancer Hospital of Shantou University Medical College, Shantou, China
- 5the Second Affiliated Hospital of Shantou University Medical College, Shantou, China
- 6Sichuan Provincial People's Hospital Jinniu Hospital, Chengdu, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Objectives Regulatory T (Treg) cells may become dysregulated in Checkpoint blockade-related inflammatory arthritis (CBIA), and we aimed to profile phenotypes and cytokine-secreting patterns of Tregs in CBIA. Methods Using a 77-protein panel, we here profiled and compared single-cell membrane proteomics of Treg cells in synovial fluid (SF) in 15 patients with active CBIA onset, 12 patients with active rheumatoid arthritis (RA), and 9 CBI-treated cancer patients with non-autoimmune inflammatory knee swelling. Microbead-sorted Treg subsets from CBIA patients underwent 32-cytokine panel secretome analysis. Peripheral blood (PB) Tregs from 7 CBIA and 6 RA patients were similarly analyzed. Findings were correlated with modified Clinical Disease Activity Index (mCDAI) in CBIA patients. Results Unsupervised clustering revealed two atypical immune-activating Treg cell clusters common to both CBIA and RA patients, in which a immuno-activating (featuring ICOS+CD134+CD137+) cluster was distinct to CBIA patients. This immuno-activating cluster was found to have a positive correlation to the mCDAI in CBIA patients. In single-cell secreting proteomics of SF-derived Treg cells in CBIA patients, we found that clusters distinct to the immuno-activating cell group featured inflammatory cytokine secretion of mainly MCP1 and MCP4, which was validated by Peripheral CBIA secreting proteomics (vs. RA, which preferentially secreted CCL11/CXCL10). Other non-immuno-activating cells mainly secreted immune-modulatory cytokines of IL10, IL4, and TGFB1. Consistently, MCP1/MCP4+polysecreting cluster proportion was also positively correlated with mCDAI. Conclusion At single-cell proteomic level, an atypical, MCP1/MCP4+polysecreting immuno-activating Treg cell type is found to have a strong relation to clinical disease activity of CBIA.
Keywords: Immune-related adverse events, Inflammatory arthritis, regulatory T cells, Single-cell proteomics, Cytokine secretion
Received: 14 May 2025; Accepted: 21 Aug 2025.
Copyright: © 2025 He, Zhou, Wu, Lin, Zhou, Gu, Wang, Wang, Mo and Lv. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Chuanzhu Lv, Sichuan Provincial People's Hospital Jinniu Hospital, Chengdu, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.