Polyfunctional endogenous EBV-specific T cell response in nasopharyngeal carcinoma

Abstract

Abstract Nasopharyngeal carcinoma (NPC) is associated with Epstein-Barr virus (EBV) infection and can be treated by adoptive transfer of EBV-specific T cells. Although EBV-specific T cell immune response has been identified in NPC, the phenotype and functionality of EBV-specific, tissue-resident memory T cells has not been explored. Tumor-infiltrating lymphocytes (TILs) were isolated from newly-diagnosed NPC and two types of EBV-unrelated malignancies; oral squamous cell carcinoma (OSCC) and renal cell carcinoma (RCC) tissue samples. We found that endogenous EBV-specific T cell response can be detected in the all the tissue types, including NPC, OSCC and RCC, but were rare in peripheral blood. In all tissues, EBV-specific T cells in tumor tissues exhibit resident memory phenotype characterized by high CD69 and CD103 expression and also an exhaustion phenotype characterized by high CD39 and PD-1 expression. Unexpectedly, EBV-specific T cell frequency as well as response magnitude were not enhanced in NPC when compared to other tissue types. The lack of an enhanced EBV-specific T cell response magnitude in NPC tissue confirms the concept that enhancement of EBV-specific immunity by adoptive T cell therapy may improve the outcome of NPC.