OX40/OX40L protein expression in non-small cell lung cancer and its role in clinical outcome and relationships with other immune biomarkers

Abstract

Abstract Background Anti-tumoral immunotherapy of anti- programmed cell death protein-1 (PD-1)/programmed cell death protein-ligand 1 (PD-L1) immune checkpoint therapy demonstrated the efficacy and tolerability in patients with lung cancer. Apart from inhibitory checkpoints, OX40, the co-stimulatory receptor related to T cell priming and proliferation, was valued identically. In this study, the relationship between OX40/OX40L among PD-1/PD-L1 and other immunological factors, as well as its role serving as the potential prognostic biomarker were analyzed in NSCLC. Methods We investigated the relationship between OX40/OX40L, PD-1/PD-L1 and TILs in surgical samples from 139 patients with NSCLC by immunohistochemistry (IHC). Factors related to OX40/OX40L expression were analyzed by logistic regression and multi-linear regression. Cox analysis was also performed to find the influencing factors. Survival analysis was conducted in order to testify its role in predicting patients’ prognosis. Results The TILs OX40/OX40L expression was negatively correlated with the PD-1/PD-L1 expression. PD-1expression was negatively correlated with the TILs OX40 expression (R\xa0=\xa00.250, [p\xa0=\xa00.003]), it was also negatively correlated with the TILs OX40L expression (R\xa0=\xa00.386, [p\xa0=\xa00.0001]). PD-1expression was positively correlated with TILs grades and negatively correlated with the TILs OX40L expression (R\xa0=\xa00.531, [X1, 95%CI 3.552-8.176, p\xa0=\xa00.0001; X2, 95%CI 0.216-0.683], [p\xa0=\xa00.0001]). The expression of TILs OX40 varied significantly among tumor OX40, OX40L, PD-1, PD-L1, TILs and pathology types. Tumor OX40L expression, TILs OX40L expression, PD-1 expression, PD-L1 expression and TILs were considered as risk factors for TILs OX40 expression. The staging and TILs OX40L were considered as risk factors for overall survival (OS) while stage and gender were risk factors for recurrence-free survival (RFS). The low-expression of OX40 was related to longer RFS, OS and better prognosis. Conclusions OX40 plays a pivotal role in NSCLC, which was closely correlated with immunological factors, RFS and prognosis. Legal entity responsible for the study The authors. Funding This study was supported in part by a grant from National Natural Science Foundation of China (81802255), Shanghai Pujiang Program (17PJD036) and a grant from Shanghai Municipal Commission of Health and Family Planning Program (20174Y0131). National key research & development project (2016YFC0902300). Major disease clinical skills enhancement program of three year action plan for promoting clinical skills and clinical innovation in municipal hospitals, Shanghai Shen Kang Hospital Development Center Clinical Research Plan of SHDC (16CR1001A). The fundamental research funds for the central universities. Disclosure All authors have declared no conflicts of interest.