Hypothesis of a CD137/Eomes activating axis for effector T cells in HPV oropharyngeal cancers

Abstract

Chronic Human Papilloma Virus (HPV) infection is supplanting alcohol and tobacco intoxications as the leading cause of oropharyngeal cancer in developed countries. HPV-related squamous cell carcinomas of the oropharynx (HPV + OSC) present better survival and respond better to radiotherapy and chemotherapy. Regulatory T cells (T_REG) are mainly described as immunosuppressive and protumoral in most solid cancers. However, T_REG are paradoxically associated with a better prognosis in HPV + OSCs. The transcription factor FoxP3 is the basis for the identification of T_REG. Among CD4 + FoxP3 + T cells, some have effector functions. A medical hypothesis is formulated here: the existence of a CD137 (4.1BB)-Eomesodermin (Eomes) activated pathway downstream of TCR-specific activation in a subpopulation of CD4 + FoxP3 + T cells may explain this effector function. Evidence suggest that this axis may exist either in CD4 + FoxP3 + T cells or CD8 + T cells. This pathway could lead T cells to strong antitumor cytotoxic activity in a tumor-specific manner. Furthermore, CD137 is one of the most expected targets for the development of agonist immunotherapies. The identification of CD137 + Eomes + FoxP3+/- T cells could be a key element in the selective activation of the most anti-tumor cells in the HPV + OSC microenvironment.

Keywords: Cancer; Eomes; FoxP3+; HPV; Lymphocytes; Squamous cell carcinoma; T regulator.

Fig. 1

Medical hypothesis of a TCR-dependant activation axis via CD137 and transcription factor Eomesodermin (Eomes) in CD4 + FoxP3 + T cells. The Figure was partly generated using Servier Medical Art®, provided by Servier, licensed under a Creative Commons Attribution 3.0 imported license