Immune Phenotypes of Nasopharyngeal Cancer

SIMPLE SUMMARY: As for many solid cancers, nasopharyngeal cancer (NPC) interacts with the immune system. In this retrospective study, immune features of NPC were explored and assessed against Epstein-Barr virus status, clinical stage, and survival. Specific immune phenotypes were identified based on presence and distribution of CD8+ T-cells: i.e., “inflamed”, “excluded”, and “deserted” NPC, which carried important prognostic information. Presence and distribution of CD207+ cells, likely representing antigen-presenting dendritic cells, were demonstrated, suggesting a potential for immune cell targeting. Gene expression revealed differences in immune profiles between NPC and control tissue as well as between subgroups of NPC based on CD8 expression (high vs. low). Taken together, the observations may be of relevance to prognostication of NPC as well as for explorations into the field of immunotherapy. ABSTRACT: Nasopharyngeal cancer (NPC) features intralesional immune cells, but data are lacking on presence/distribution of T-cells and dendritic cells (DCs). Based on intralesional distribution of lymphocytes, a series of NPC biopsies (n = 48) were classified into “inflamed”, “excluded”, and “deserted” phenotypes. In addition, CD8+ T-cells and CD207+ DCs were quantified. The data were analyzed in relation to Epstein–Barr virus-encoded small RNA (EBER), Epstein-Barr virus (EBV) DNA, and survival. Separately, data on gene expression from a public database were analyzed. 61.7% of NPC lesions were “inflamed”, 29.8% were “excluded”, and 8.5% were “deserted”. While CD8+ cells were present in cancer cell areas and in surrounding stroma, CD207+ cells were observed largely in cancer cell areas. High CD8+ T-cell presence was associated with EBV+ disease, but no such pattern was observed for CD207+ DCs. There was a difference in disease-free survival in favor of “inflamed” over “excluded” NPC. Gene expression analysis revealed differences between NPC and control tissue (e.g., with regard to interferon activity) as well as between subgroups of NPC based on CD8 expression (high vs. low). In conclusion, NPC lesions are heterogeneous with regard to distribution of CD8+ T-cells and CD207+ DCs. NPC can be classified into immune phenotypes that carry prognostic information. CD207+ DCs may represent a target for immunotherapy with potential to facilitate the antigen cross-presentation necessary to execute cytotoxic T-lymphocyte responses.