Prognostic influence of tumor microenvironment after hypofractionated radiation and surgery for mesothelioma.

Abstract

OBJECTIVE\nCytotoxic CD8+ tumor infiltrating lymphocytes (TILs) can contribute to the benefit of hypofractionated radiation, but programmed cell death pathways (programmed cell death 1 and programmed cell death ligand 1 [PD-1/PD-L1]) may\xa0provide a mechanism of tumor immune escape. We therefore reviewed the\xa0influence of PD-1/PD-L1 and CD8+ TILs on survival after accelerated hypofractionated hemithoracic radiation followed by extrapleural pneumonectomy for malignant pleural mesothelioma (MPM).\n\n\nMETHODS\nSixty-nine consecutive patients undergoing the protocol of Surgery for Mesothelioma after Radiation Therapy (SMART) between November 2008 and February 2016 were analyzed for the presence of PD-L1 on tumor cells, PD-1 on inflammatory cells, and CD8+ TILs. Comparison was made with a cohort of patients undergoing extrapleural pneumonectomy after induction chemotherapy (n\xa0=\xa014) and no induction (n\xa0=\xa02) between March 2005 and October 2008. PD-L1 expression on tumor cells ≥1% was considered positive. CD8+ TILs and PD-1 expression were scored as a percentage of positive cells.\n\n\nRESULTS\nPD-L1 was negative in 75% of MPM after completion of SMART. CD8+ TILs ranged between 0.24% and 8.47% (median 2%). CD8+ TILs ≥2% was associated with significantly better survival in epithelioid MPM (median survival 3.7\xa0years vs 2.3\xa0years in CD8+ TILs <2%; P\xa0=\xa0.02). PD-L1 positivity was associated with worse survival in biphasic MPM (median survival, 0.4\xa0years vs 1.5\xa0years in biphasic PD-L1 negative tumors; P\xa0=\xa0.07) after SMART. Multivariate analysis demonstrated that epithelioid MPM, nodal disease, and CD8+ TILs were independent predictors of survival after SMART.\n\n\nCONCLUSIONS\nThe influence of tumor microenvironment on survival differs between epithelioid and nonepithelioid MPM. CD8+ TILs is an independent factor associated with better survival in epithelioid MPM treated with SMART.