PD-L1 expression is associated with epithelial-mesenchymal transition in head and neck squamous cell carcinoma

// Chan-Young Ock 1, * , Sehui Kim 2, * , Bhumsuk Keam 1, 3 , Miso Kim 1 , Tae Min Kim 1, 3 , Jin-Ho Kim 4 , Yoon Kyung Jeon 2 , Ju-Seog Lee 5 , Seong Keun Kwon 6 , J. Hun Hah 6 , Tack-Kyun Kwon 6 , Dong-Wan Kim 1, 3 , Hong-Gyun Wu 4 , Myung-Whun Sung 6 , 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 Radiation Oncology, Seoul National University Hospital, Seoul, South Korea 5 Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA 6 Department of Otorhinolaryngology, Seoul National University Hospital, Seoul, South Korea * These authors have contributed equally to this work Correspondence to: Bhumsuk Keam, e-mail: bhumsuk@snu.ac.kr Keywords: PD-L1, epithelial-mesenchymal transition, head and neck, squamous, p16 Received: September 23, 2015      Accepted: February 06, 2016      Published: February 17, 2016 ABSTRACT Virus-associated malignancies and sarcomatoid cancers correlate with high PD-L1 expression, however, underlying mechanisms remain controversial. We evaluated the correlation between PD-L1 expression and epithelial-mesenchymal transition (EMT) in head and neck squamous cell carcinomas (HNSCC).Tumor tissues from 50 patients with HNSCC were evaluated for PD-L1 by immunohistochemistry, which showed 32 (64.0%) were PD-L1 positive (PD-L1+). Interestingly, PD-L1 expression was significantly associated with EMT ( P = 0.010), as assessed by low E-cadherin and high vimentin expression. The overall survival of PD-L1+ patients with EMT features was significantly worse than those without EMT features ( P = 0.007). In an independent validation cohort (N = 91), as well as in HNSCC cases of The Cancer Genome Atlas (TCGA) and the Cancer Cell Line Encyclopedia, high PD-L1 expression was also associated with the high probability of an EMT signature, referred from the GEO dataset, GSE4824. Survival analysis confirmed PD-L1+/EMT+ patients had a poorer prognosis than PD-L1+/EMT- patients in the TCGA cohort. PD-L1 positivity can thus be divided into two categories according to the absence or presence of EMT. PD-L1 expression is also independently associated with EMT features in HNSCC.