PD-L1 expression and its relationship with oncogenic drivers in non-small cell lung cancer (NSCLC)
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Liyan Jiang1,*, Xinying Su2,*, Tianwei Zhang2, Xiaolu Yin2, Meizhuo Zhang3, Haihua Fu2, Hulin Han2, Yun Sun2, Lili Dong1, Jialin Qian1, Yanhua Xu4, Xuan Fu4, Paul R. Gavine2, Yanbin Zhou5, Kun Tian 6, Jiaqi Huang7, Dong Shen7, Haiyi Jiang4, Yihong Yao7, Baohui Han1, Yi Gu2
1Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
2Asia & Emerging Markets, iMed, AstraZeneca, Shanghai, China
3R&D Information, AstraZeneca, Shanghai, China
4Global Medicines Development, AstraZeneca, Shanghai, China
5The First Affiliated Hospital, Sun Yat-Sen University, Guangdong, China
6General Hospital of Chengdu Military Region of PLA, Sichuan, China
7R&D, MedImmune, AstraZeneca, Gaithersburg, MD, USA
*These authors contributed equally to this study
Yi Gu, email: [email protected]
Baohui Han, email: [email protected]
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
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.
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