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

Yayi He; Xiaoshen Zhang; Keyi Jia; Rafal Dziadziuszko; Sha Zhao; Juan Deng; Hao Wang; Fred R Hirsch; Caicun Zhou

doi:10.21037/tlcr.2019.08.15

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

Transl Lung Cancer Res. 2019 Aug;8(4):352-366. doi: 10.21037/tlcr.2019.08.15.

Authors

Yayi He¹, Xiaoshen Zhang^{1

2}, Keyi Jia^{1

2}, Rafal Dziadziuszko³, Sha Zhao^{1

2}, Juan Deng^{1

2}, Hao Wang^{1

2}, Fred R Hirsch⁴, Caicun Zhou¹

Affiliations

¹ Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, Shanghai 200433, China.
² Tongji University, Shanghai 200433, China.
³ Department of Oncology and Radiotherapy, Medical University of Gdansk, Gdansk, Poland.
⁴ Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

Abstract

Background: Anti-tumoral immunotherapy of anti-program death-1/program death-ligand 1 (PD-1/PD-L1) immune checkpoint therapy demonstrated promising 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 expressed on tumor infiltrating lymphocytes (TILs), 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 were negatively correlated with the PD-1/PD-L1 expression, respectively. PD-1 expression was negatively correlated with the TILs OX40 expression [R=0.250, (P=0.003)], it was also negatively correlated with the TILs OX40L expression [R=0.386, (P=0.0001)]. PD-1 expression was positively correlated with TILs grades and negatively correlated with the TILs OX40L expression in multiple linear model [R=0.531, (X1, 95% CI: 3.552-8.176, P=0.0001; X2, 95% CI: 0.216-0.683), (P=0.0001)]. The expression of TILs OX40 varied significantly among tumor OX40 and 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.

Keywords: CD134; OX40; non-small cell lung cancer (NSCLC); program death-1 (PD-1); program death-ligand 1 (PD-L1).