Alterations and correlation between DNA damage and repair response and PD-L1 expression in non-small cell lung...

DNA damage and repair (DDR) is involved in the antitumor immune response, however, the correlation between DNA damage response with immunotherapy in NSCLC remain unclear. We examined the relationship between DDR alterations and expression of PD-L1 in non-small cell lung cancer.

Tumor tissues, para-carcinoma and normal tissues, were obtained from 54 patients who were surgically resected NSCLC tumors. Patient characteristics, neoplasm staging and pathological information were collected. Immunohistochemical analysis of tissue samples was analyzed for γH2AX、RAD51, PARP-1 and PD-L1 protein expression.

A total of 54 patients with non-small cell lung cancer were included in this study, including 24 males and 30 females with ages ranging from 45 to 79 years (mean, 63.5 years). The high expression rate of γH2AX staining in lung cancer was 81.5%(44/54)and the expression levels of γH2AX protein were significantly higher in NSCLC than those in paired para-carcinoma 50%(27/54) and normal tissues 42.6%(23/54). The expression levels of RAD51 protein were significantly higher in lung cancer tissue 68.5%(37/54) than those in paired para-carcinoma 48.1%(26/54) and normal tissues 40.7%(22/54). There was a significant correlation between high RAD51 expression and male patients 87.5%(21/24) (p = 0.009) and a history of smoking 90%(18/20) (p = 0.014). The presence of any DDR alteration was showed with PD-L1. (1) HigherγH2AX expression was observed in the PD-L1 positive cases 90.6% (29/32) compared to the PD-L1 negative cases 68.2% (15/22). Lung cancers with higher γH2AX expression were associated with the higher expression of PD-L1 (p = 0.046, r = 0.284). (2) There was no statistically significant correlation between expression of PD-L1 and RAD51 (p = 0.221, r = 0.168). (3) Higher PARP-1 expression was observed in the PD-L1 negative cases 59.1% (13/22) compared to the PD-L1 positive cases 25% (8/32). Lung cancers with higher PARP-1 expression were associated with the lower expression of PD-L1 (p = 0.009, r=-0.344). (4) No statistically significant association was observed in relationship between expression of DDR Expression (γH2AX、RAD51) and PARP-1 of patients (p = 0.507 and p = 0.817,respectively).

Overall, our study shows that high expression of γH2AX, RAD51, and PARP1 proteins display in NSCLC and proves that DNA damage repair may be closely related to the occurrence and development of NSCLC. γH2AX could be a predictor of the adaptation of ICIs as an alternative to PD-L1, and NSCLC is expected to benefit from PARP-1 inhibitors combined with immunotherapy.