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.

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. 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. 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). 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.

Hu B ，Sun M ，Wang Z ，Zheng Y ，Cai W ，Shi HH ，Zhuang Y ，Lin Q ... -  《-》

Prognostic stratification of patients with nasopharyngeal carcinoma based on tumor immune microenvironment.

Little is known about immune-related prognostic factors in patients with nasopharyngeal carcinoma (NPC). We retrospectively reviewed 66 patients with NPC. Epstein-Barr virus (EBV) status, programmed cell death-ligand 1 (PD-L1) expression, and tumor-infiltrating lymphocyte (TIL) densities were analyzed, and a prognostic evaluation of these immune-related parameters was performed. The multivariate analyses demonstrated that CD8-positive TIL density but not PD-L1 expression on tumor cells or immune cells was a significant predictive factor for progression-free survival (PFS) and overall survival (OS). Subgroup analyses demonstrated that a positive PD-L1 expression on tumor cells in combination with a higher CD8-positive TIL density was significantly associated with favorable prognosis, whereas positive PD-L1 expression on tumor cells with lower CD8-positive TIL density was associated with worse prognosis. Our results suggest that PD-L1 expression on tumor cells in combination with CD8-positive TIL density could be a useful predictive biomarker for risk stratification in patients with NPC.

Ono T ，Azuma K ，Kawahara A ，Sasada T ，Matsuo N ，Kakuma T ，Kamimura H ，Maeda R ，Hattori C ，On K ，Nagata K ，Sato F ，Chitose SI ，Shin B ，Aso T ，Akiba J ，Umeno H ... -  《-》

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

Larbcharoensub N ，Mahaprom K ，Jiarpinitnun C ，Trachu N ，Tubthong N ，Pattaranutaporn P ，Sirachainan E ，Ngamphaiboon N ... -  《-》

PD-L1 predicts poor prognosis for nasopharyngeal carcinoma irrespective of PD-1 and EBV-DNA load.

Zhou Y ，Shi D ，Miao J ，Wu H ，Chen J ，Zhou X ，Hu D ，Zhao C ，Deng W ，Xie C ... -  《Scientific Reports》

Expression of Immune Checkpoint Regulators, Cytotoxic T-Lymphocyte Antigen-4, and Programmed Death-Ligand 1 in Epstein-Barr Virus-associated Nasopharyngeal Carcinoma.

Nasopharyngeal carcinoma (NPC) is the most common cancer arising from the nasopharynx with a poor prognosis. Targeting immune checkpoint is one of the new promising lines in cancer treatment. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death-ligand 1 (PD-L1) are immune checkpoints that regulate T-cell immune function. This work aimed to assess the immunohistochemical expression of PD-L1 and CTLA-4 in NPC and their ability to predict survival and response therapy and to check their validity as immunotherapy targets. Twenty-six cases of NPC were studied by immunohistochemistry for PD-L1 and CTLA-4 and by nested polymerase chain reaction followed by DNA sequencing for the presence of EBNA-1 gene of Epstein-Barr virus (EBV). All investigated cases were diagnosed and treated in the Zagazig University Hospital in the period from August 2015 to July 2018. EBNA-1 gene was identified in 84.6% of the cases. Whereas the expression of PD-L1 was noted in 46.2% of all cases studied, 54.6% of EBV-associated NPCs were found to express PD-L1. There was a significant association between PD-L1 expression and the advanced stage of the tumor (P<0.001). CTLA-4 expression was observed in 88.4% of all NPC cases as cytoplasmic staining in both tumor cells and tumor-infiltrating lymphocytes. CTLA-4 expression in lymphocytes was associated with the presence of EBV. A significant association was detected between CTLA-4 and tumor-infiltrating lymphocyte expression on one side and the stage of the tumor on the other. High expression of CTLA-4 was significantly associated with disease progression and worse overall survival. PD-L1 and CTLA-4 are adverse prognostic markers in NPC. The authors propose that targeted therapy against PD-L1 and CTLA-4 will be a hopeful therapy for cases of NPC with resistance to concurrent chemoradiation treatment in Egypt, especially EBV-associated cases.

Ahmed MM ，Gebriel MG ，Morad EA ，Saber IM ，Elwan A ，Salah M ，Fakhr AE ，Shalaby AM ，Alabiad MA ... -  《-》