Regulatory T cells expressing abundant CTLA‐4 on the cell surface with a proliferative gene profile are key features of human head and neck cancer

FOXP3⁺ regulatory T (Treg) cells suppress anti‐tumor immunity. The suppression of Treg cells is regulated by cytotoxic T‐lymphocyte‐associated antigen‐4 (CTLA‐4), whose expression on the cell surface is tightly regulated. Here we found that Treg cells expressing abundant CTLA‐4 on the cell surface (surface‐CTLA‐4⁺ Treg) were expanded in human head and neck cancer tissues. RNA sequencing of surface‐CTLA‐4⁺ and surface‐CTLA‐4^– Treg cells infiltrating human head and neck cancer tissues revealed that surface‐CTLA‐4⁺ Treg cells have a previously undescribed gene expression profile correlating to cell cycle, cell proliferation, and DNA replication. Moreover, surface‐CTLA‐4⁺ Treg cells were PD‐1⁺, actively proliferated and associated with CD45RA^‐ FOXP3^high Treg cells with strong suppressive function. Thus, surface‐CTLA‐4⁺ Treg cells with a proliferative gene expression signature and phenotype are key features of head and neck cancer. Targeting surface‐CTLA‐4⁺ Treg cells might be new strategies to evoke effective immune responses to head and neck cancer.

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