DOK1 and DOK2 regulate CD8 + T cell signaling and memory formation without affecting tumor cell killing
In: https://amu.hal.science/hal-03623067 ; 2022, 2022
report
Zugriff:
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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DOK1 and DOK2 regulate CD8 + T cell signaling and memory formation without affecting tumor cell killing
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Autor/in / Beteiligte Person: | Laletin, V. ; Bernard, P. L. ; Montersino, C. ; Yamanashi, Y. ; Olive, D. ; Castellano, R. ; Guittard, G. ; Nunès, J., A ; Centre de Recherche en Cancérologie de Marseille (CRCM) ; Aix Marseille Université (AMU)-Institut Paoli-Calmettes (IPC) ; Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
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Zeitschrift: | https://amu.hal.science/hal-03623067 ; 2022, 2022 |
Veröffentlichung: | HAL CCSD, 2022 |
Medientyp: | report |
DOI: | 10.1101/2021.12.17.473111 |
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