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Article Dans Une Revue Molecular Medicine Année : 2024

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

Robin Baudouin
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Cécile Badoual
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Stéphane Hans
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Résumé

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.
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hal-04583607 , version 1 (22-05-2024)

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Robin Baudouin, Eric Tartour, Cécile Badoual, Stéphane Hans. Hypothesis of a CD137/Eomes activating axis for effector T cells in HPV oropharyngeal cancers. Molecular Medicine, 2024, 30 (1), pp.26. ⟨10.1186/s10020-024-00796-w⟩. ⟨hal-04583607⟩

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