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Neuronal autoantibodies have been identified in immune-mediated encephalitis, most of which are related to paraneoplastic neurologic syndromes (PNS). We detected neuronal autoantibodies in patients with gastric cancer without PNS and illustrated their correlation with clinical prognosis. All serum samples were tested by the mouse brain tissue-based assay (TBA) using immunofluorescence for screening neuronal autoantibodies. Known PNS-related neuronal autoantibodies were detected by cell-based assay. A single-center cohort has been started in Nanfang Hospital. The T-cell status of the tumor microenvironment was assessed. Single-cell sequencing was performed with limited tumor samples. Patients were grouped into TBA-positive (n = 144) and TBA-negative (n = 179) groups by the TBA status. Further screening of TBA+ specimens using the cell-based assay method revealed known PNS-related autoantibodies in 13.2% (19/144) of cases. Additionally, TBA-positive patients with gastric cancer exhibited lower CD8+ T-cell infiltration in the tumor tissue. The survival analysis show that neuronal autoantibodies in patients (TBA-positive) were associated with shorter overall survival (OS; P = 0.014). In the multivariate survival analysis, TBA positivity was still associated with shortened OS after adjusting the major covariates (HR = 2.28; 95% confidence interval, 1.31-3.97; P = 0.004). Meanwhile, single-cell sequencing indicates that cell junction assembly and synapse organization may play important roles in biological process. In this cohort study, neuronal autoantibodies were highly prevalent among patients with gastric cancer and were associated with shortened OS and features of immunosuppression within the tumor microenvironment, suggesting a candidate for exploring therapeutic relevance, with further mechanistic studies needed for validation.

Neuronal autoantibodies are prevalent in patients with gastric cancer, and patients without neurologic symptoms are linked to shorter survival and immunosuppression. These results provide a new direction for prognostic biomarkers and targeted therapy exploration.