Human Leukocyte Antigen Class I and Programmed Death-Ligand 1 Coexpression 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. 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 = .033, p = .007, and p = .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 < .001, p = .002, and p = .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 = .001). Multivariate analysis revealed that coexpression of HLA class I and PD-L1 was an independent poor prognostic factor of lung adenocarcinoma. (p < .001; hazard ratio, 6.106; 95% confidence interval, 2.260 to 16.501). CONCLUSIONS: Lung adenocarcinoma with coexpression of HLA class I and PD-L1 was associated with poor prognosis. This subgroup may evade immune attack by expressing PD-L1 protein despite HLA expression.

HLA and lung transplantation / 医学前沿

Lung transplantation is increasingly practiced for patients with end-stage lung disease. The successful outcome of solid organ transplantation today is severely impeded by the production of alloantibodies, mainly directed against the protein products of the HLA complex of the organ donor. While the association between antibody mediated rejection and allograft damage has been well established in renal and heart transplantation, it has not yet been well characterized in lung transplantation. This review addresses the question of HLA matching in lung transplantation and current knowledge of the allogenicity of different HLA class I and II antigens. The role of the antibody mediated immune response is discussed as well as the importance of pre-transplant or de novo post-transplant circulating antibodies. Finally, potential mechanisms, which may act individually or in combination, of antibody mediated damage to solid organ transplants are considered.

A study on human leukocyte antigen class I molecules in paediatric bronchial asthma.

Childhood asthma, often associated with atopy, is more common in boys and may persist throughout life in 50% of cases. This case-control study was carried out to examine if any association of paediatric bronchial asthma with human leukocyte antigen (HLA) class I antigens. Thirty-six children with bronchial asthma diagnosed on basis of Global Initiative for Asthma (GINA) criteria and an equal number of healthy controls without history of bronchial asthma were studied. Low resolution HLA- ABC typing was performed by sequence specific primers (SSP) and the frequency of HLA–ABC antigens in the two groups was compared. Total serum immunoglobulin E (IgE) estimation was done as a marker of atopy by ELISA. The study included 24 boys and 12 girls aged 13 months to 11 yrs, of which 16 (44%) had positive family history. Serum IgE levels were elevated in 20 (55%) of the cases and 33% of controls with peak values of 4877 and 627 IU/ml, respectively. No statistically significant correlation was observed between childhood asthma and HLA class I antigens, however, a statistically significant correlation was observed between serum IgE levels and asthma, which was elevated in cases, as compared to normal population. Serum IgE levels did not show a linear trend, in that a direct correlation with the severity of disease was not observed.