Abstract

Lung cancer is the most commonly diagnosed cancer and also the leading cause of cancer death globally. Chemotherapy showed limited improvement in the survival of surgically resected non-small cell lung cancer (NSCLC) patients. There was no effective prognostic indicators in surgically resected NSCLC. The expression levels of tumor surface molecules, such as major histocompatibility complex class I (MHC-I), programmed cell death-ligand 1 (PD-L1) and CD8+ tumor infiltrating lymphocytes (TILs) were detected in this study to investigate the potential prognostic markers in the patients with surgically resected NSCLC. Tissue of 125 patients with surgically resected NSCLC were obtained from the First Hospital of Jilin University. MHC-I, PD-L1 and CD8+ TILs expressions were detected with immunohistochemistry. The association between their expression levels and patients’ prognosis was analyzed by SPSS 17.0 software. MHC-I was down-expressed, PD-L1 was up-regulated in NSCLC compared with the adjacent tissues. CD8+ TILs could be seen in tumor stroma and nest. With univariate analysis, we found that the down-expression of MHC-I had an association with poor relapse-free survival (RFS) and overall survival (OS) in NSCLC patients (P = 0.007 and P = 0.001). RFS and OS in PD-L1− group tended to be longer than that of PD-L1+ group, but the difference was not significant (P > 0.05). Based on the distribution of CD8+ TILs, patients were divided into three groups: immune-inflamed group, immune-excluded group and immune-desert group. RFS and OS of patients with the immune-inflamed phenotype (CD8inflamed) were longer than patients with the immune-excluded and immune-desert phenotype (CD8non-inflamed) (P = 0.013 and P = 0.015). Besides, patients were divided into four subgroups based on the PD-L1 and CD8+ TILs expression: PD-L1+/CD8inflamed, PD-L1+/CD8non-inflamed, PD-L1−/CD8inflamed, and PD-L1−/CD8non-inflamed. Statistical differences were achieved both in RFS and OS (P = 0.012 and P = 0.032). RFS and OS in patients with PD-L1+/CD8inflamedandPD-L1−/CD8inflamed were longer than patients with PD-L1+/CD8non-inflamed andPD-L1−/CD8non-inflamed. Patients with PD-L1+/CD8non-inflamed experienced the worst RFS and OS. With multivariate analysis, we found that MHC-I and CD8+ TILs might be independent prognostic factors in surgically resected NSCLC. MHC-I and CD8+ TILs expression had a close association with patients prognosis in this study. The combination of PD-L1 and CD8+ TILs, instead of PD-L1 alone, suggested impressive prognostic values in NSCLC patients. It worth further study to confirm the clinical value of MHC-I, PD-L1 and CD8 TILs expressions in the patients with surgically resected NSCLC.

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