Prognostic Value of Programmed Cell Death-Ligand 1 Expression in Tumor-Infiltrating Lymphocytes and Viral Load in Peripheral Blood Mononuclear Cells for Epstein–Barr Virus–Positive Nasopharyngeal Carcinoma

• Published in: Clinical chemistry (Baltimore, Md.) Vol. 66; no. 9; pp. 1219 - 1227
• Main Authors: Hu, Bin, Sun, Ming, Wang, Zijin, Zheng, Yanping, Cai, Weifeng, Shi, Helen Hsiao-Hsing, Zhuang, Yanzhen, Lin, Qin
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01-09-2020; American Association for Clinical Chemistry, Inc
• Subjects: Adolescent; Adult; Aged; Apoptosis; B cells; B7-H1 Antigen - analysis; Biomarkers, Tumor - analysis; Blood; Blood levels; Cancer; Carcinoma; Cell death; Deoxyribonucleic acid; Development and progression; DNA; Epstein-Barr virus; Ethylenediaminetetraacetic acid; Female; Gene expression; Health aspects; Herpesvirus 4, Human; Humans; Immunohistochemistry; Immunotherapy; Leukocytes (mononuclear); Leukocytes, Mononuclear - virology; Lymphocytes; Lymphocytes, Tumor-Infiltrating - virology; Male; Medical prognosis; Medical research; Medicine, Experimental; Metastases; Middle Aged; Nasopharyngeal carcinoma; Nasopharyngeal Carcinoma - diagnosis; Nasopharyngeal Carcinoma - virology; Nasopharyngeal Neoplasms - diagnosis; Nasopharyngeal Neoplasms - virology; Patients; PD-L1 protein; Peripheral blood mononuclear cells; Prognosis; Progression-Free Survival; Risk groups; Throat cancer; Tumor-infiltrating lymphocytes; Tumors; Viral Load; Viruses; Young Adult; China; Nasopharyngeal carcinoma; PD-L1; EBV DNA; droplet digital PCR; recurrence and metastasis; TIL
• ISSN: 0009-9147; 1530-8561
• DOI: 10.1093/clinchem/hvaa170

Abstract
Background
Epstein–Barr virus (EBV) infection has a role in the development and progression of nasopharyngeal carcinoma (NPC); however, it is unclear whether EBV load correlates with tumor prognosis or the need for immunotherapy. This study evaluated whether the EBV DNA concentration in peripheral blood mononuclear cells (PBMC) or programmed cell death-ligand1 (PD-L1) expression in tumor-infiltrating lymphocytes (TIL) could predict the clinical outcomes of patients with NPC.
Methods
Clinicopathological parameters of 198 patients with NPC were analyzed retrospectively from June 2012 to May 2018. Patients’ EBV loads were determined by droplet digital PCR. TIL PD-L1 was analyzed by immunohistochemistry.
Results
A log value of 1.98 log IU/mL for PBMC EBV DNA and a percentage of PD-L1 expression of 15% in TILs marked distinguishing cutoffs in NPC prognosis. The 5-year progression-free survival (PFS) rates in patients with high vs low log (PBMC EBV DNA) were 68.2% and 93.1%, respectively (P = 0.002). The 5-year PFS rates in patients with high vs low TIL PD-L1 expression were 66.3% and 33.7%, respectively (P = 0.03). The 5-year PFS rates of the high-risk group (high log [PBMC EBV DNA] and low TIL PD-L1), low-risk group (low log [PBMC EBV DNA] and high TIL PD-L1), and those in between (intermediate group) were 0%, 91.9%, and 71.4%, respectively (P < 0.001).
Conclusion
Concentrations of PBMC EBV DNA and TIL PD-L1 expression can be used as prognostic markers in NPC. The combination of both an increased EBV DNA concentration and suppressed TIL PD-L1 expression is associated with metastasis or relapse.