细胞毒T淋巴细胞相关抗原4（CTLA-4）是介导肿瘤免疫逃逸的重要抑制性分子。抗CTLA-4单抗具有治疗肺癌的作用，其联合治疗的应用价值受到关注。课题组前期研究显示益气养阴解毒方改善机体细胞免疫功能，下调肺癌患者外周血中与CTLA-4生物学效应相同的可溶性CTLA-4（sCTLA-4）表达。基于此，提出“益气养阴解毒方联合抗CTLA-4单抗协同诱导抗肺癌免疫应答”的假说。拟用免疫细胞共培养、小鼠肺癌原位移植瘤模型研究益气养阴解毒方联合抗CTLA-4单抗的协同抗癌作用，对T细胞亚群免疫功能状态影响，对效应和调节性T细胞表面CTLA-4及sCTLA-4的下调作用；并通过PI3K/Akt通路探讨益气养阴解毒方联合抗CTLA-4单抗协同增强T细胞免疫应答的分子机制。从免疫检查点角度揭示益气养阴解毒方发挥作用的生物学基础及其与免疫靶向治疗联合应用的价值，丰富“扶正治癌”以提高自身抗癌能力的作用内涵。

Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is an important inhibitory molecule that mediates tumor immune escape. Treatment of lung cancer with anti-CTLA-4 monoclonal antibody has been proved to be effective, and the value of anti-CTLA-4 monoclonal antibody combined with other therapies of lung cancer should be paid more attention. The preliminary study shows that Yiqi Yangyin Jiedu decoction can improve the cellular immune function and down-regulate the expression of soluble CTLA-4 (sCTLA-4) sharing the same biological effects with CTLA-4 in peripheral blood of patients with lung cancer. In light of this, we put forward the hypothesis that “Yiqi Yangyin Jiedu decoction combined with anti-CTLA-4 monoclonal antibody enhances immune response against lung cancer”. Immunocyte co-culture and a system of orthotopic transplantation tumor model of lung cancer in mice will be used to study the impact of Yiqi Yangyin Jiedu decoction combined with anti-CTLA-4 monoclonal antibody on lung cancer , the immune function of T cell subsets and the expression of CTLA-4 on effector and regulatory T Cells. We will research into the molecular mechanism of synergistic enhancement of T cell immune response by anti-CTLA-4 monoclonal antibody combined with Yiqi Yangyin Jiedu decoction through PI3K/Akt pathway. This study will reveal the biological basis of the role of Yiqi Yangyin Jiedu decoction and the importance of its combination with immune targeted therapy from the perspective of immune checkpoint so as to advance the mechanism of “treating tumor by improving the general condition”.