High-titer antinuclear antibodies are associated with severe immune-related toxicity and exploratory survival outcomes in advanced gastric cancer immunotherapy
In brief
High-titer ANA raises severe immune toxicity risk eightfold in gastric cancer
In a retrospective cohort of 244 advanced gastric cancer patients treated with checkpoint inhibitors, 17.6% had ANA titers at least 1:160 and were about eight times more likely to develop grade 3-4 immune-related adverse events. Organ-specific antibodies were rare and did not predict toxicity; a possible link to longer progression-free survival was seen but remains exploratory.
- Journal
- Therapeutic advances in medical oncology (Q1)
- Published
- 6 August 2026
- Study design
- Prospective / inception cohort
- Evidence level
- Level 2, Moderate (CEBM 2b)
- Authors
- Wanrong Liu, Hui Tang, Ningning Li, Wei Qiu, Xiaoyuan Li, Lin Zhao
- PMID
- 42571170
- DOI
- 10.1177/17588359261476860
Why clinicians should know about it
- Picked for Oncology and Radiation Oncology (paper of the day, 10 August 2026): High‑titer ANA predicts severe irAEs in advanced gastric cancer immunotherapy
Abstract
BACKGROUND: Clinicians often screen for autoantibodies before initiating immune checkpoint inhibitors (ICIs) in advanced gastric cancer (GC), yet the utility of organ-specific panels remains unclear. OBJECTIVES: To evaluate the association of baseline antinuclear antibody (ANA) titers and organ-specific autoantibodies with severe immune-related adverse events (irAEs) and clinical outcomes in patients with advanced GC receiving ICIs. DESIGN: Single-center retrospective cohort study. METHODS: We retrospectively analyzed 244 patients with advanced GC treated with ICIs. Baseline ANA titers and organ-specific antibodies, including Ro52, thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb), were systematically evaluated. Associations with grade 3-4 irAEs were assessed using Firth's penalized logistic regression. Progression-free survival (PFS) was analyzed using Kaplan-Meier methods, Cox proportional hazards regression, subgroup analyses, and propensity score matching. RESULTS: The prevalence of organ-specific antibodies was low (<7%) and failed to predict toxicity. In contrast, high-titer ANA (≥1:160, 17.6% of patients) predicted grade 3-4 irAEs (OR = 7.98, 95% CI: 3.35-19.5; p < 0.001). Although the high-titer ANA group included a numerically higher proportion of PD-L1-negative tumors, exploratory survival analyses showed longer PFS in patients with high-titer ANA in univariable analysis (p = 0.038), whereas the association was attenuated after multivariable adjustment (adjusted HR = 0.60, 95% CI: 0.35-1.01, p = 0.056) and remained borderline after propensity score matching (p = 0.049). CONCLUSIONS: High-titer ANA was associated with an increased risk of severe irAEs in patients with advanced GC receiving ICIs. Its association with longer PFS was exploratory and requires prospective validation. These findings suggest that ANA titers may help baseline toxicity risk stratification, whereas routine screening for low-yield organ-specific autoantibodies may offer limited clinical utility in unselected patients.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.