Human Leukocyte Antigen Class I and Programmed Death-Ligand 1 Co-expression Is an Independent Poor Prognostic Factor in Adenocarcinoma of the Lung.

Background: Both human leukocyte antigen (HLA) class I and programmed death-ligand 1 (PD-L1) molecules are known to play important roles in cancer immunity. In this study, we evaluated HLA class I expression in resected adenocarcinoma of the lung, and investigated its prognostic impact in correlation with PD-L1 expression.

Materials and Methods: HLA class I and PD-L1 expression was evaluated by immunohistochemistry in a total of 403 resected lung adenocarcinomas using tissue microarray. Correlations between the expression of HLA class I/PD-L1 and clinicopathologic features and prognostic significance were analyzed.

Results: HLA class I expression was reduced in 91.6% of adenocarcinoma, and more frequently reduced in patients with younger age, absence of vascular invasion, and low pathologic stage (p=0.033, p=0.007 and p=0.012, respectively). Positive PD-L1 expression in tumor cells was 16.1% (1% cut-off), and associated with poor differentiation, presence of vascular invasion and nodal metastasis (p<0.001, p=0.002 and p=0.032, respectively). On survival analysis, HLA class I or PD-L1 expression alone did not show any statistical significance. On the integrated analysis, HLA class I (+)/PD-L1 (+) subgroup showed a significantly shorter overall survival than other groups (p=0.001). Multivariate analysis revealed that co-expression of HLA class I and PD-L1 was an independent poor prognostic factor of lung adenocarcinoma. (p<0.001, Hazard ratio=6.106 with 95% confidence interval 2.260-16.501).

Conclusion: Lung adenocarcinoma with co-expression of HLA class I and PD-L1 was associated with poor prognosis. This subgroup may evade immune attack by expressing PD-L1 protein despite of HLA expression.