PD-L1 expression and its relationship with oncogenic drivers in non-small cell lung cancer (NSCLC)

// Liyan Jiang 1, * , Xinying Su 2, * , Tianwei Zhang 2 , Xiaolu Yin 2 , Meizhuo Zhang 3 , Haihua Fu 2 , Hulin Han 2 , Yun Sun 2 , Lili Dong 1 , Jialin Qian 1 , Yanhua Xu 4 , Xuan Fu 4 , Paul R. Gavine 2 , Yanbin Zhou 5 , Kun Tian 6 , Jiaqi Huang 7 , Dong Shen 7 , Haiyi Jiang 4 , Yihong Yao 7 , Baohui Han 1 , Yi Gu 2 1 Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China 2 Asia & Emerging Markets, iMed, AstraZeneca, Shanghai, China 3 R&D Information, AstraZeneca, Shanghai, China 4 Global Medicines Development, AstraZeneca, Shanghai, China 5 The First Affiliated Hospital, Sun Yat-Sen University, Guangdong, China 6 General Hospital of Chengdu Military Region of PLA, Sichuan, China 7 R&D, MedImmune, AstraZeneca, Gaithersburg, MD, USA * These authors contributed equally to this study Correspondence to: Yi Gu, email: yigu68@yahoo.com Baohui Han, email: xkyyhan@gmail.com Keywords: PD-L1, non-small cell lung cancer (NSCLC), biomarker, tumor-infiltrating immune cells, oncogenic driver Received: August 02, 2016      Accepted: February 20, 2017      Published: March 01, 2017 ABSTRACT In order to explore the potential patient population who could benefit from anti PD-1/PD-L1 mono or combination therapies, this study aimed to profile a panel of immunotherapy related biomarkers (PD-1, PD-L1, CTLA-4 and CD8) and targeted therapy biomarkers (EGFR, KRAS, ALK, ROS1 and MET) in NSCLC. Tumor samples from 297 NSCLC patients, including 156 adenocarcinomas (AD) and 129 squamous cell carcinomas (SCC), were analyzed using immunohistochemistry, immunofluorescence, sequencing and fluorescence in situ hybridization. 43.1% of NSCLC patients had PD-L1 positive staining on ≥ 5% tumor cells (TC). Furthermore, dual color immunofluorescence revealed that the majority of PD-L1/CD8 dual positive tumor infiltrating lymphocytes (TIL) had infiltrated into the tumor core. Finally, combined analysis of all eight biomarkers showed that tumor PD-L1 positivity overlapped with known alterations in NSCLC oncogenic tumor drivers in 26% of SCC and 76% of AD samples. Our illustration of the eight biomarkers’ overlap provides an intuitive overview of NSCLC for personalized therapeutic strategies using anti-PD-1/PD-L1 immune therapies, either as single agents, or in combination with targeted therapies. For the first time, we also report that PD-L1 and CD8 dual positive TILs are predominantly located within the tumor core.