Department of Otolaryngology-Head & Neck Surgery, Foch Hospital, 40 rue Worth, 92 150, Suresnes, France.
School of Medicine, UFR Simone Veil, Université Versailles Saint-Quentin-en- Yvelines (Paris Saclay University), 2 Av. de la Source de la Bièvre, Montigny- le-Bretonneux, 78 180, France.
Mol Med. 2024 Feb 14;30(1):26. doi: 10.1186/s10020-024-00796-w.
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) are mainly described as immunosuppressive and protumoral in most solid cancers. However, T are paradoxically associated with a better prognosis in HPV + OSCs. The transcription factor FoxP3 is the basis for the identification of T. 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.
慢性人乳头瘤病毒（HPV）感染正在取代酒精和烟草中毒，成为发达国家口咽癌的主要病因。与 HPV 相关的口咽鳞状细胞癌（HPV+OSC）的生存率更高，对放疗和化疗的反应更好。调节性 T 细胞（T）在大多数实体瘤中主要被描述为免疫抑制和促肿瘤。然而，T 与 HPV+OSC 中的更好预后相关。转录因子 FoxP3 是鉴定 T 的基础。在 CD4+FoxP3+T 细胞中，一些具有效应功能。这里提出了一个医学假设：在 TCR 特异性激活的亚群中，下游存在 CD137（4.1BB）-Eomesodermin（Eomes）激活途径，可能解释了这种效应功能。有证据表明，该轴可能存在于 CD4+FoxP3+T 细胞或 CD8+T 细胞中。该途径可以使 T 细胞以肿瘤特异性方式产生强烈的抗肿瘤细胞毒性活性。此外，CD137 是开发激动剂免疫疗法最有希望的靶点之一。CD137+Eomes+FoxP3+/-T 细胞的鉴定可能是在 HPV+OSC 微环境中选择性激活最抗肿瘤细胞的关键因素。
