Development of novel combined cancer immunotherapy using adoptive naive T cell transfer.

在过继性细胞疗法（ACT）中，转移的细胞群体的内在特性，特别是其分化状态，被认为是基于ACT的方法的成功的关键，并且初始T细胞由于其体内持久性和高增殖潜力而对于ACT是理想的。考虑到小鼠结肠癌模型中转移细胞的分化状态，我们评估了CTLA-4阻断与ACT组合的协同抗肿瘤作用。4阻断结合幼稚T细胞转移显示出所有组中最强的抗肿瘤作用。此外，CTLA-4阻断剂可使肿瘤浸润性T细胞向辅助性T细胞1分化，抑制肿瘤内T淋巴细胞的表达，尤其是与初始T细胞联合应用时，这些数据支持了CTLA-4阻断剂与含有大量初始T细胞的ACT联合应用在临床上具有强大的抗肿瘤作用的观点。

In adoptive cell therapy(ACT), the intrinsic properties of the transferred cell population, particularly its state of differentiation, are considered to be crucial to the success of ACT based approaches, and naive T cells are ideal for ACT because of their in vivo persistence and high proliferative potential.In this study, we evaluated the synergic anti-tumor effect of CTLA-4 blockade combined with ACT considering the state of differentiation of transferred cells in mouse colon cancer model.CTLA-4 blockade combined with naive T-cell transfer showed the strongest antitumor effect among all groups. Moreover, CTLA-4 blockade can drive polarization of tumor-infiltrating T cells toward the T helper 1 lineage and suppress the frequency of Tregs within tumor especially in combination with naive T-cell transfer.These data support the notion that the combination of CTLA-4 blockade and ACT containing a lot of naive cells could expert powerful antitumor effects in clinical setting.