Characterization of PD-L1 and PD-1 Expression and CD8+ Tumor-infiltrating Lymphocyte in Epstein-Barr Virus-associated Nasopharyngeal Carcinoma

Objectives: Immunotherapies that target the programmed death-1/ programmed death-1 ligand (PD-1/PD-L1) immune checkpoint pathway have shown promise in nasopharyngeal carcinoma (NPC) in early phases clinical studies. Here, we evaluated PD-1 and PD-L1 expression and CD8+ tumor-infiltrating lymphocytes (TILs) in NPC patients. Materials and Methods: Newly diagnosed NPC patients were identified through the institutional database between January 2007 and December 2012. PD-L1 and PD-1 expression, Epstein-Barr virus (EBV) status, and CD8+ TIL numbers were measured in archival tumor samples at diagnosis and their correlations with clinicopathologic features, including survival, were evaluated. Results: A total of 114 NPC patients were analyzed. Most patients (96%) were EBV positive. PD-L1 was expressed in ≥1% of tumor cells (TCs) in 69% of patients, in ≥50% of TCs in 12% of patients, and in ≥5% of either TCs or infiltrating immune cells in 71% of patients. CD8+ TILs were present in tumors from all patients, whereas only 11% of tumors expressed PD-1. There were no correlations between PD-L1 expression and CD8+ TIL abundance, PD-1 expression, or survival. Conclusions: Approximately 70% of EBV-positive NPC expressed PD-L1, but this did not correlate with patient survival or clinicopathologic features. The findings of this study represent the immune biomarker profile of confirmed EBV-associated NPC in an endemic region. Since the current clinical development of immune checkpoint inhibitor for NPC is mostly focusing on an EBV-associated tumor, differences in immune biomarker profiles and EBV status of endemic and nonendemic regions should be further explored. N.L. and K.M. contributed equally. Supported by the Ramathibodi Cancer Center grant. N.N. received funding from the Research University Network (RUN) and Talent Management Program of Mahidol University, and the Ramathibodi Grant for Research Development from Ramathibodi Hospital. An abstract of this work was presented at the 2015 ASCO Annual Meeting, May 29 to June 2, 2015, Chicago, IL. The authors declare no conflicts of interest. Reprints: Nuttapong Ngamphaiboon, MD, Department of Medicine, Division of Medical Oncology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, 270 Rama VI Road, Ratchathewi, Bangkok 10400, Thailand. E-mail: nuttapong.nga@mahidol.ac.th. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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