Association of neuronal autoantibodies with overall survival in gastric cancer patients

Neuronal autoantibodies have been identified in immune-mediated encephalitis, and most of which are related to paraneoplastic neurological syndromes (PNS). We detected neuronal autoantibodies in gastric cancer patients 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 (CBA). A single-center cohort has been started in Nanfang hospital. T cells status of the tumor microenvironment was assessed. Singel 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 CBA method revealed known PNS-related autoantibodies in 13.2% (19/144) of cases. Additionally, TBA positive gastric cancer patients 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 OS (P=0.014). In the multivariate survival analysis, TBA positive was still associated with shortened OS after adjusting the major covariates (HR = 2.28, 95% CI: 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 gastric cancer patients 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 to validation.