Prognostic role of tumor infiltrating lymphocytes in EBV positive and EBV negative nasopharyngeal carcinoma

Abstract

Objectives: Tumor infiltrating lymphocytes (TILs) correlate with both better and worse prognosis in solid tumors. As therapeutic modalities for nasopharyngeal carcinoma (NPC) are limited, immunotherapy could be a potential alternative. Up till now there is limited prognostic data on the role of TILs in NPC, so we assessed the prognostic role of TILs in Epstein-Barr-virus (EBV) positive and negative NPC.

Methods: Tissue of 92 NPCs was assessed for CD3, CD4, CD8, PD1 and PDL1 expression in the tumor's micro-environment. Correlations between clinicopathological characteristics was assessed using the Pearson X² test, Fisher's exact test and ANOVA. Survival was analyzed with the Kaplan-Meier method and Cox regression. Differences in CD3, CD4, CD8, PD1, PDL1 counts/(co)expression between EBV positive and negative NPCs were evaluated using the Mann-Whitney U test. Two-tailed P values below 0.05 were considered statistically significant.

Results: EBV positive NPC contains significantly more CD3, CD4 and CD8 TILs than EBV negative NPC. In the whole NPC group, increased CD8 count is associated with better overall survival (OS) (HR 0.219 (95%CI 0.075-0.640)), but also in cases with PDL1 co-expression (HR 0.073 (95%CI 0.010-0.556)). In EBV positive NPC co-expression of CD8 and PDL1 showed better disease free survival (HR 0.407 (95%CI 0.195-0.850)) and OS (HR 0.170 (95%CI 0.037-0.787)).

Conclusions: Although TILs are significantly different between EBV positive and negative NPCs, it is especially composition of the infiltrate which determines prognosis. Effects of PD1 and CD8 need more study, because these findings show much potential in using immunotherapeutic modalities in NPC treatment.

Keywords: EBV; Epstein Barr virus; NPC; Nasopharyngeal carcinoma; Tumor-infiltrating lymphocytes.