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

Abstract : ABSTRACT Targeting intracellular inhibiting proteins is a promising strategy to improve CD8 + T cell anti-tumor efficacy. DOK1 and DOK2 are CD8 + T cell inhibitory proteins that are targeted in this study in order to improve the activation and cytotoxic capacities of these cells. To evaluate the role of DOK-1 and DOK-2 depletion in physiology and effector function of T CD8 + lymphocyte and in cancer progression, a transgenic T cell receptor mouse model specific to melanoma antigen hgp100 (pmel-1 TCR Tg) was established. Depletion of both Dok1 and Dok2 did not affect the development, proliferation, mortality, activation and cytotoxic function of naive CD8 + T cells. However, after an in vitro pre-stimulation Dok1 / Dok2 DKO CD8 + T cells had higher percentage of effector memory T cells and showed an increase in levels of pAKT and pERK upon TCR stimulation. Despite this improved TCR signaling, pre-stimulated Dok1 / Dok2 DKO CD8 + T cells did not show any increase in their activation or cytotoxicity capacities against melanoma cell line expressing hgp100 in vitro . Altogether we demonstrate here a novel aspect of the negative regulation by DOK1 and DOK2 proteins in CD8 + T cells. In conclusion, DOK1 and DOK2 have an inhibitory role following long term T cell stimulations.
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Preprints, Working Papers, ...
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Contributor : Jacques A NUNES Connect in order to contact the contributor
Submitted on : Tuesday, March 29, 2022 - 2:28:17 PM
Last modification on : Wednesday, March 30, 2022 - 1:52:43 PM

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V. Laletin, P.-L. Bernard, C. Montersino, Y. Yamanashi, D. Olive, et al.. DOK1 and DOK2 regulate CD8 + T cell signaling and memory formation without affecting tumor cell killing. 2022. ⟨hal-03623067⟩



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