Cancer germline antigens and tumor-agnostic CD8+ T cell evasion

Abstract

Cancer germline antigens (CGAs) are expressed in immune-privileged germline tissues, while epigenetically silenced in somatic tissues. CGAs become re-expressed in tumors and can promote oncogenesis. Tumors prominently exploit mechanisms similar to those in germline tissues to shield from immunosurveillance. We hypothesize that CGAs contribute towards tumor escape from immune effector CD8⁺ T cells. For illustrative purposes, we assessed the co-presence or -absence of CGAs with these cells in multiple tumor types. Considering a broad array of CD8⁺ T cell evasive mechanisms, we exemplify the co-occurrence of gene transcripts of eight CGAs with those of adhesion molecules, endothelial cells, and/or the Wnt pathway. We present a novel concept of CGAs and their association with CD8⁺ T cell evasion, which may be relevant for future immunotherapeutic interventions.

Keywords: CD8(+) T cell evasion; T cell function; T cell influx; antigen recognition by T cells; cancer germline antigens (CGAs); pan-cancer; tumor infiltrating lymphocytes (TILs).