为了剖析新辅助PD-1和CTLA4抑制在未经治疗的头颈鳞状细胞癌中对肿瘤内部T细胞的影响，我们分析了治疗反应和非反应患者的原发性肿瘤免疫浸润。在基线上，活跃（4-1BB/OX-40+）和非活跃调节性CD4+ T细胞之间的比例较高与免疫治疗反应相关。此外，在治疗过程中，反应患者中这种活跃的调节性T细胞群体明显减少。在类似的过程中，反应患者内肿瘤内部功能障碍的CD8+ T细胞表达的活性和功能相关基因下降，而在临床非反应者中，NK细胞在治疗早期显示出增加的细胞毒作用。这些数据揭示了对双重PD-1/CTLA4抑制的免疫学变化，包括对应答患者中推测的肿瘤反应性调节性T细胞和CD8+ T细胞区域的平行重塑，并表明基线时激活的调节性T细胞的存在可能与治疗反应相关联。

To dissect the effect of neoadjuvant PD-1 and CTLA4 blockade on intratumoral T cells in treatment-naive head and neck squamous cell carcinoma, we analyzed primary tumor immune infiltrates from responding and non-responding patients. At baseline, a higher ratio between active (4-1BB/OX-40+) and inactive regulatory CD4+ T cells was associated with immunotherapy response. Furthermore, upon therapy, this active Treg population showed a profound decrease in responding patients. In an analogous process, intratumoral dysfunctional CD8+ T cells displayed decreased expression of activity and dysfunction-related genes in responding patients, while in clinical non-responders NK cells showed an increased cytotoxic profile early upon treatment. These data reveal immunological changes in response to dual PD-1/CTLA4 blockade, including a parallel remodeling of presumed tumor-reactive Treg and CD8+ T cell compartments in responding patients, and indicate that the presence of activated Tregs at baseline may be associated with response.