J Cancer 2017; 8(19):4075-4082. doi:10.7150/jca.21415

Research Paper

Programmed cell death ligand 1 protein levels predicted survival of non-small cell lung cancer

Shaohua Cui1*, Xinying Su2*, Lili Dong1, Jialin Qian1, Lin Ye1, Tianwei Zhang2, Haihua Fu2, Hulin Han2, Jiaqi Huang3, Yihong Yao3, Yi Gu2, Liyan Jiang1✉

1. Department of Respiratory Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
2. Asia & Emerging Markets, iMed, AstraZeneca, Shanghai, China
3. R&D, MedImmune, AstraZeneca, Gaithersburg, MD, USA
*Shaohua Cui and Xinying Su contributed equally to this study.

Abstract

Objective: To investigate the relationship between programmed death ligand 1 (PD-L1) expression using 5%, 25%, 50% cutoffs in tumor cells (TC) and postsurgical survival in non-small-cell lung cancer (NSCLC) patients. For samples with tumor infiltrating lymphocytes (TIL), correlation between PD-L1 expression in TIL using 1% cutoff and postsurgical survival was also evaluated.

Methods: Primary NSCLC tumor surgical samples staging I to IIIA of 126 patients who underwent surgical procedures from September 2009 to August 2012 in Shanghai Chest Hospital, Shanghai Jiao Tong University were retrospectively included. PD-L1 protein expression was detected by immunohistochemistry (IHC) assays. A rabbit anti-human PD-L1 (E1L3N) monoclonal antibody (1:300, CST#13684, Cell Signaling Technology) was used for PD-L1 IHC staining. PD-L1 expression was evaluated both on TC and TIL. Univariate and multivariate analyses for postsurgical survival were done using Kaplan-Meier and Cox regression model, respectively.

Results: The median postsurgical survival for all patients was 44.1 months [95% confidence interval (CI): 33.9-70.0 months). The median postsurgical survival for PD-L1 expression percentage 0, 1-50% and ≥50% were 51.9 months (95%CI: 33.9-70.0 months), 33.2 months (95%CI: 20.8-45.6 months) and 14.7 months (95%CI: 1.9-27.6 months), respectively (P = 0.002). Clinical stage and PD-L1 expression in TC (25% cutoff or 50% cutoff values) were found to be independent predictors for longer postsurgical survival in all cohort. Ninety (71.4%) of the 126 samples were identified to concurrent TIL. The median postsurgical survival time was 39.6 months (95% CI: 31.8-47.4 months) in patients with TIL. PD-L1 expression in TC (25% cutoff or 50% cutoff values) was found to be the independent predictor for longer postsurgical survival time in patients with TIL.

Conclusion: PD-L1 negative expression in TC at 25% or 50% cutoff values was the independent predictor for longer postsurgical survival time in both NSCLC samples and NSCLC samples with TIL. For patients with PD-L1 high expression at 25% or 50% cutoff values, PD-L1 blocking may be considered.

Keywords: Programmed death ligand 1 (PD-L1), non-small-cell lung cancer (NSCLC), tumor cells (TC), tumor infiltrating lymphocytes (TIL), survival

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How to cite this article:
Cui S, Su X, Dong L, Qian J, Ye L, Zhang T, Fu H, Han H, Huang J, Yao Y, Gu Y, Jiang L. Programmed cell death ligand 1 protein levels predicted survival of non-small cell lung cancer. J Cancer 2017; 8(19):4075-4082. doi:10.7150/jca.21415. Available from http://www.jcancer.org/v08p4075.htm