Changes in programmed death-ligand 1 expression during cisplatin treatment in patients with head and neck squamous cell carcinoma

Abstract

// Chan-Young Ock 1 , Sehui Kim 2 , Bhumsuk Keam 1, 3 , Soyeon Kim 3 , Yong-Oon Ahn 3 , Eun-Jae Chung 4 , Jin-Ho Kim 5 , Tae Min Kim 1, 3 , Seong Keun Kwon 4 , Yoon Kyung Jeon 2 , Kyeong Chun Jung 2 , Dong-Wan Kim 1, 3 , Hong-Gyun Wu 5 , Myung-Whun Sung 4 and Dae Seog Heo 1, 3 1 Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea 2 Department of Pathology, Seoul National University Hospital, Seoul, Korea 3 Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea 4 Department of Otorhinolaryngology, Seoul National University Hospital, Seoul, Korea 5 Department of Radiation Oncology, Seoul National University Hospital, Seoul, Korea Correspondence to: Bhumsuk Keam, email: bhumsuk@snu.ac.kr Keywords: programmed death-ligand 1, head and neck squamous cell carcinoma, cisplatin Received: February 22, 2017      Accepted: June 04, 2017      Published: June 16, 2017 ABSTRACT Programmed death-ligand 1 (PD-L1) expression is regarded as a predictive marker for anti-PD-1/PD-L1 therapy. The purpose of study was to explore the changes in PD-L1 expression in head and neck squamous cell carcinoma (HNSCC) during treatment. Paired HNSCC tissues prior to and after cisplatin-based treatment were evaluated to determine PD-L1 protein expression by immunohistochemistry. Among the 35 HNSCC patient samples, PD-L1 expression status changed after treatment in 37.1% (13/35) of samples. Among the 13 patients whose baseline PD-L1 was negative, PD-L1 expression was increased in 9 cases (69.2%) and remained negative in 4 cases (30.8%, P = 0.003). Patients exposed to cisplatin generally showed PD-L1 up-regulation (83.3%, P = 0.037) compared to those not exposed to cisplatin (57.1%, P = 0.072). To validate these findings in vitro , changes in PD-L1 expression in HNSCC cell lines (Detroit-562, PCI-13, SNU-1041, SNU-1066, SNU-1076, and FaDu) were analyzed by western blotting and flow cytometry after treatment with cisplatin and interferon-gamma. In HNSCC cell lines, PD-L1 expression was significantly up-regulated after cisplatin, along with phosphor-MAPK/ERK kinase up-regulation. In conclusion, PD-L1 expression in HNSCC may be altered during cisplatin treatment, activating the MAPK/ERK kinase pathway.