Improved Prognosis and Increased Tumor-Infiltrating Lymphocytes in Patients Who Have SCLC With Neurologic Paraneoplastic Syndromes.

Iams WT, Shiuan E, Meador CB, Roth M, Bordeaux J, Vaupel C, Boyd KL, Summitt IB, Wang LL, Schneider JT, Warner JL, Zhao Z, Lovly CM
J Thorac Oncol. 2019 14 (11): 1970-1981

PMID: 31201935 · PMCID: PMC6823126 · DOI:10.1016/j.jtho.2019.05.042

BACKGROUND - Approximately 10% of patients with 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 patients who have SCLC 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 programmed death 1 (PD-1)/programmed death ligand 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 compared to patients with endocrinologic PNS and controls (median overall survival of 24 months versus 12 months versus 13 months, 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.

CONCLUSIONS - Tumor tissue from patients with SCLC with neurologic PNS showed increased tumor-infiltrating lymphocytes and PD-1/PD-L1 interaction consistent with an inflamed tumor microenvironment.

Copyright © 2019 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

MeSH Terms (15)

Aged B7-H1 Antigen Biomarkers, Tumor Female Humans Lung Neoplasms Lymphocytes, Tumor-Infiltrating Male Middle Aged Paraneoplastic Syndromes, Nervous System Prognosis Retrospective Studies Small Cell Lung Carcinoma Survival Rate Tumor Microenvironment

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