肿瘤免疫逃逸机制之一是CD8 + T细胞高表达程序死亡蛋白-1（PD-1），导致免疫无能。免疫检查点（如PD-1）抑制剂在肿瘤免疫治疗中已取得一定临床效果，但同时显示对部分病人无效。为什么存在脱靶效应？其原因及靶标仍不完全清楚。我们回输自体培养毒性淋巴细胞（CTL）治疗大肠癌，部分病人肝转移病灶减少，部分病人CD8+T细胞PD-1水平增加；体外研究显示阻断PD-1/PD-L1后，CTL活性和向肿瘤细胞的趋化性增强，但有部分CTL不反应，推测存在其他相关靶标如TIGIT/CD226 pairs, TIM3等参与肿瘤细胞逃逸过程。我们将深入分析PD-1表达与免疫治疗的关系、抗PD-1抗体联合过继性免疫治疗作用机理，并结合荷瘤动物模型进一步研究脱靶原因，及这些标靶之间的相互作用，及在阻断PD-1/PD-L1过程中的作用。预期将寻找新的目标蛋白，联合使用，提高肿瘤过继性免疫治疗有效性及病人生存期。

Colorectal cancer is the third most common cause of death due to cancer in the world. Tumour escape is major concern during T cells recruitment under microenvironment due to higher expression of programme death-1 (PD-1) on CD8+ T cells, which cause immune anergy. The exhausted tumour specific T cells express high level of PD-1 and that blockade of the PD-1 pathways can enhance in vitro T cell responses. Monoclonal-antibody-based therapies targeting PD-1 (checkpoint blockade) have yielded significant clinical benefits including durable responses to patients with different malignancies. The effectiveness of single cancer immunotherapy remains quite low in clinical trials. Our preliminary results indicate CTLs based adoptive adoptive immunotherapy reduce liver metastatic lesion in CT-scan images, on the contrary PD-1 level increased on CD8 T cells. So, we used blocked PD-1/PD-L1 that enhance CTLs activity, and enhanced chemotactic infiltration in vitro experiments. Selective CTLs were ineffective in killing tumour cells after PD-1/PD-L1 blockade which indicates direct involvement of related targets such as TIGIT/CD226 pairs, TIM3 and ICOS etc. Our aim is to find off target of therapeutic anti PD-1, which possibly responsible for effectiveness of adoptive immunotherapy in clinical application. We will find new target that involve during PD-1/PD-L1 blockade, and enhance effectiveness of adoptive immunotherapy either in single or combinations.