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

在过继细胞治疗(ACT)中，转移细胞群体的固有特性，特别是其分化状态，被认为是基于ACT的方法成功的关键，而初始T细胞因其在体内的持久性和高增殖潜能而成为ACT的理想细胞。在本研究中，我们评估了CTLA-4阻断联合ACT在小鼠结肠癌模型中的协同抗肿瘤作用。CTLA-4阻断联合初始T细胞转移显示出最强的抗肿瘤作用。此外，阻断CTLA-4可以促使肿瘤浸润性T细胞向辅助性T细胞1方向极化，并抑制肿瘤内Tregs的频率，特别是与初始T细胞转移相结合。这些数据支持了CTLA-4阻断与含有大量初始细胞的ACT相结合可以在临床上发挥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.