ArticleFrontiers in immunology2026
Clinical characteristics of immune-related adverse events after immune checkpoint inhibitor therapy with or without chemotherapy in patients with antinuclear antibody-positive malignancies.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Antinuclear antibodies (ANA) are detected in cancer patients before ICI therapy, but their association with immune-related adverse events (irAEs) and outcomes is uncertain. This study aimed to characterize irAEs and tolerability in ANA-positive patients receiving ICI ± chemotherapy, and explore implications for resistance. Methods: We retrospectively analyzed 121 solid tumor patients who received ICI therapy ± chemotherapy at the China-Japan Union Hospital (2021-2026). By baseline ANA titer (≥1:80 positive), patients were divided into positive (n=60) and negative (n=61) groups. We compared the incidence, severity, onset time, organ distribution, glucocorticoid use, and immunotherapy outcomes of irAEs between the two groups. Results: The incidence of irAEs was significantly higher in the ANA-positive group than in the ANA-negative group (70.0% vs. 49.2%, OR = 2.41, 95% CI: 1.14-5.09, P = 0.026). A significant dose-response relationship was observed between ANA titer and irAE risk (P_trend = 0.036), and each increase in titer category was associated with an 80% increase in risk (OR = 1.80). Autoantibody burden associated positively with irAE incidence (0 positive: 54.84%; 1 positive: 72.73%; ≥2 positive: 83.33%), although irAE severity did not increase with antibody burden (P = 0.581). The ANA positive group showed a trend toward higher irAE rates across multiple organ systems, including endocrine, pulmonary, and hepatic toxicities. There was no significant difference in the proportion of patients who discontinued ICIs because of irAEs between the two groups (20.0% vs. 21.3%, P = 1.000), and glucocorticoid use was also similar (33.3% vs. 23.3%, P = 0.357). Notably, the ANA-positive group showed a lower proportion of discontinuation due to disease progression (21.6% vs. 34.4%, P = 0.157), suggesting a potential link to delayed chemoresistance. Conclusion: Baseline ANA positivity may be a potential predictor of irAE development after ICI therapy with or without chemotherapy and shows a clear dose effect relationship. ANA-positive patients exhibited a clinical pattern characterized by a high frequency but manageable irAEs; under standardized management, this did not compromise treatment continuity and may indicate stronger antitumor immune activation with potential survival benefit,potentially delaying acquired resistance to ICIs. Baseline autoantibody testing may help identify high-risk patients and guide resistance-overcoming monitoring strategies.
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