Targeting of Novel Pathways in Chronically Activated T Cells Prevents Their Functional Exhaustion

In cancer, persistent antigenic challenge leads to T cells acquiring a hyporesponsive cell state, also referred to as T cell exhaustion. We have previously demonstrated that human CD3
+ T cells repeatedly stimulated in vitro via their TCR, develop phenotypical characteristics of exhausted T cells found in vivo including increased expression of inhibitory receptors PD-1, TIM-3 and LAG3 and diminished responsiveness to dendritic cell activation and cancer cell cytotoxicity. We showed that PD-1 blockade with nivolumab and treatment with an IKZF3 inhibitor, lenalidomide reinvigorated the exhausted T cells. 1 We next wished to evaluate if blocking of IKZF3 during the development of T cell exhaustion could protect them from acquiring the exhausted phenotype and functional hyporesponsiveness.

Fill in the form to download the poster.

Please fill in this form to access the full resource