DOK1 and DOK2 regulate CD8 T cell signaling and memory formation without affecting tumor cell killing.

ABSTRACT: Targeting intracellular inhibiting proteins has been revealed to be a promising strategy to improve CD8⁺ T cell anti-tumor efficacy. Here, we are focusing on intracellular inhibiting proteins specific to TCR signaling: DOK1 and DOK2 expressed in T cells. We hypothesized that depletion of intracellular inhibition checkpoint DOK1 and DOK2 could improve CD8⁺ T-cell based cancer therapies. To evaluate the role of DOK1 and DOK2 depletion in physiology and effector function of CD8⁺ T lymphocytes and in cancer progression, we established a transgenic T cell receptor mouse model specific to melanoma antigen hgp100 (pmel-1 TCR Tg) in WT and Dok1/Dok2 DKO (double KO) mice. We showed that both DOK1 and DOK2 depletion in CD8⁺ T cells after an in vitro pre-st

SUBMITTER: Laletin V 

PROVIDER: S-EPMC11220026 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature