调节性T细胞（Treg）可通过抑制宿主抗肿瘤免疫反应促进肿瘤的进展，然而近年研究显示Treg存在三类独立的功能异质性亚群。我们前期研究报道：Treg亚群中，仅活化型CD45RA-FOXP3hiTreg（aTreg）与头颈鳞癌的进展密切相关。近期预实验结果显示头颈鳞癌肿瘤微环境中的Treg以aTreg表型为主，提示肿瘤微环境aTreg介导了头颈鳞癌免疫逃逸；同时，我们发现头颈鳞癌患者外周血aTreg特异性表达趋化因子受体CCR4。推测：头颈鳞癌aTreg在CCR4辅助下募集至肿瘤微环境，进而通过抑制宿主抗肿瘤免疫反应促进肿瘤进展。本研究将在前期研究基础上，进一步明确CCR4对头颈鳞癌aTreg的关键趋化作用；探讨aTreg对肿瘤特异性T细胞的免疫抑制作用；体内实验验证以CCR4为靶点阻断aTreg肿瘤微环境浸润可有效抑制肿瘤进展。本课题将为以aTreg为靶点的头颈鳞癌免疫治疗提供合理的依据

Regulatory T cells (Treg) contribute to the progression of head and neck squamous cell carcinoma (HNSCC) by suppressing antitumor immunity. However, recent study showed that human Treg can be dissected into three functionally distinct subsets. We previously reported that within these Treg subsets, only activated CD45RA-FOXP3hiTreg (aTreg) are significantly related to HNSCC development. Our recent pre experimental results showed that tumor microenvironment Treg exhibit an aTreg phenotype, suggesting that aTreg in tumor microenvironment play an important role in immune escape of HNSCC; meanwhile, aTreg from peripheral blood of HNSCC patients specifically expressed chemokine receptor CCR4. We hypothesized that HNSCC aTreg are recruited into tumor microenvironment with the help of CCR4, and then promote tumor progression by inhibiting host antitumor immune response. Based on our previous studies, this study will further clarify the key role of CCR4 in HNSCC aTreg recruitment; investigate the effect of aTreg on the immune suppression of tumor specific T cells; confirm that blockade of tumor infiltrating aTreg via CCR4 targeting can effectively inhibit HNSCC progression in vitro. This study will provide reasonable evidence for aTreg-targeting immunotherapy of HNSCC.