Improved prognosis and increased tumor infiltrating lymphocytes in small cell lung cancer patients with neurologic paraneoplastic syndromes

Abstract Background Approximately 10% of patients with small cell lung cancer (SCLC) develop a paraneoplastic syndrome (PNS). Neurologic PNS are thought to improve prognosis, which we hypothesized is related to increased tumor infiltrating lymphocytes and immune recognition. Methods We queried 2,512,042 medical records from a single institution to identify SCLC patients with and without PNS and performed manual, retrospective chart review. We then performed multiplexed fluorescence immunohistochemistry and automated quantitative analysis (AQUA® Technology) on tumors to assess CD3, CD4, and CD8 T cell infiltrates and PD-1/PD-L1 interactions. T cell infiltrates and PD-1/PD-L1 interaction scores were compared among patients with neurologic PNS, endocrinologic PNS, and a control group without PNS. Clinical outcomes were analyzed using the Kaplan-Meier method and Cox proportional-hazards models. Results We evaluated 145 SCLC patients: 55 with PNS (25 neurologic and 30 endocrinologic) and 90 controls. Patients with neurologic PNS experienced improved overall survival (OS) compared to patients with endocrinologic PNS and controls (median OS 24mo vs. 12mo vs. 13mo, respectively). Of the 145 patients, we identified tumor tissue from 34 patients that was adequate for AQUA analysis. Among 37 specimens from these 34 patients, patients with neurologic PNS had increased T cell infiltrates (p=0.033) and PD-1/PD-L1 interaction (p=0.014) compared to tumors from patients with endocrinologic PNS or controls. Conclusion Tumor tissue from patients with SCLC with neurologic PNS demonstrated increased tumor infiltrating lymphocytes and PD-1/PD-L1 interaction consistent with an inflamed tumor microenvironment.