Prognostic value of the expression of immunomodulatory targets in surgically resected lung adenocarcinoma.

Abstract

173 Background: Therapies targeting immune checkpoints have recently shown encouraging activity in patients with non-small cell lung cancer. T-cell activation is controlled by the balance of co-stimulatory molecules that act positively in concert with T-cell receptor (TCR) signaling induced by antigen stimulation and co-inhibitory molecules (immune checkpoint molecules) that negatively regulate TCR signaling. Methods: We performed a Cap Analysis of Gene Expression (CAGE) analysis to quantify the gene expression of PD-L1, PD-L2, co-inhibitory molecules (CTLA-4, PD-1, TIM-3, BTLA, VISTA and LAG-3) and co-stimulatory molecules (CD28, OX40, GITR, CD317, CD27 and HVEM) using RNA extracted from 71 frozen tumor tissue samples of surgically resected lung adenocarcinomas, including 35 EGFR-mutated, 11 KRAS-mutated and 25 wild-type tumors. The correlations between the expression of the above immunomodulatory targets and the overall survival were analyzed. None of patients received immunotherapy. Results: Lung adenocarcinomas in this study were divided into two groups: tumors showing high expression of almost all immunomodulatory targets and those with low expression. The expression of CTLA-4, PD-1 and PD-L1 was not prognostic. The prognosis of patients with tumors showing high expression of TIM-3 was significantly worse than that of those with low expression, regardless of the EGFR and KRAS mutation status. The prognosis of patients with tumors showing high expression of VISTA was significantly better than that of those with low expression, regardless of the EGFR and KRAS mutation status. The prognosis of patients with tumors showing high expression of LAG-3 was significantly worse than that of those with low expression among overall patients. However, high expression of LAG-3 was an unfavorable prognostic factor in patients with EGFR-mutated or wild-type tumors, and it was a favorable prognostic factor in patients with KRAS-mutated tumors. Conclusions: Lung adenocarcinomas may be divisible into immunogenic and nonimmunogenic tumors. The prognostic value differs according to the immunomodulatory target and driver oncogene status.