ORIGINAL RESEARCH article
Front. Oncol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research TopicAutoantibodies in Cancer: Diagnostic, Prognostic, and Therapeutic PotentialView all 6 articles
Serum Autoantibody Profiles in Cancer Patients Treated with Immune Checkpoint Inhibitors: A Cross-Sectional Study
Provisionally accepted
- Beijing Cancer Hospital, Beijing, China
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Background: The relationship between autoantibody profiles and immune checkpoint inhibitor (ICI) therapy in cancer patients remains incompletely characterized. This cross-sectional study investigated serum autoantibody (AAb) prevalence and profiles across multiple tumor types before and after ICI therapy. Methods: This study analyzed serum autoantibodies in 808 participants: 358 treatment-naïve cancer patients (ICI-group), 250 cancer patients following ≥6 months of ICI therapy (ICI+ group), and 200 healthy controls (HC). The cancer cohort comprised 10 solid tumor types. Serum samples were analyzed for antinuclear antibodies (ANA), antiphospholipid antibodies (aPL), anti-neutrophil cytoplasmic antibodies (ANCA), and anti-thyroid antibodies (ATA) using automated quantitative immunoassays. Results: Cancer patients demonstrated significantly elevated AAb prevalence compared to healthy controls. The ICI− group showed positivity rates of 20.1% for ANA, 11.5% for aPL, 1.7% for ANCA, and 17.3% for ATA, compared to 10.5%, 4.5%, 1.5%, and 9.5% in healthy controls, respectively. After ICI therapy, ANA positivity increased to 33.6%. CTLA-4 inhibitor recipients demonstrated higher ANA frequencies than PD-1/PD-L1 monotherapy recipients (57.1% vs 27.1%,). Tumor stage did not significantly influence AAb prevalence. Colorectal, hepatocellular, and renal cancers showed significant ANA increases after ICI treatment. Anti-Scl-70, anti-SSA-60, and anti-RNP were the most frequently elevated ANA subtypes. Anti-thyroglobulin was the most responsive ATA subtype following ICI therapy. Conclusions: ANA profiles vary across tumor types and differ between treatment-naïve and ICI-treated patients. CTLA-4-treated patients exhibit higher ANA frequency. Different tumors exhibit distinct preferences for AAb expression patterns. Serum AAb profiling may serve as a valuable tool for immunotherapy monitoring and risk stratification for immune-related adverse events.
Keywords: Autoantibody, Antinuclear antibody, Cancers, Immune checkpoint inhibitor, Immunotherapy
Received: 30 Sep 2025; Accepted: 06 Nov 2025.
Copyright: © 2025 Chen, Guo, Liu, Wang, Zhang and Xu. 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: Guobing Xu, bjzlxgb@163.com
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