Immune surveillance was defined as three phases during tumorigenesis: elimination, equilibrium and escape. During the escape phase, cancer cell acquire a series of mechanism to evade the recognition by immune system, including reduce the function of antigen presenting cells, recruitment of suppressive cells, induce T cell exhaustion etc. The exhaustion phenotype of T cells were frequently observed in various cancer types and exhibit as reduced effector cytokine production, decrease in proliferation and cytolytic activity and overexpression of inhibitory receptors. Restoring T cell exhaustion phenotype become the inspiring filed for cancer therapy and PD1 blocking antibody further encouraging the concept of intervention on T cell exhausted phenotype in tumor microenvironment. In this study, we utilize human primary T cell to establish the in vitro model of T cell exhaustion. Subsequent functional study reveal that the induced exhausted T cell (Tex) display significantly weak response towards dendritic cell activation compare to normal T cell (Tnorm). We take advantage of the model to validate the function of PD1 antibody and demonstrate that blocking of PD1 could partially restore the function of Tex, which suggesting there are still other regulators involved in mediating T cell exhaustion beyond PD1.

Citation Format: Tienan Wang, Jie Zhang, Zhijun Wang, Yingnian Li, Linghong Shi, Qing Lin. Establishment of in vitro human T cell exhaustion model to enable high throughput target validation for T cell phenotype restoring [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2774.