Nicotinamide Inhibits T Cell Exhaustion and Increases Differentiation of CD8 Effector T Cells

Nicotinamide Inhibits T Cell Exhaustion and Increases Differentiation of CD8 Effector T Cells.

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Item Type: Article
Status: Published
Official URL:
Journal or Publication Title: Cancers
Volume: 14
Number: 2
Page Range: p. 323
Date: 2022
Divisions: Melanoma Epigenetics Laboratory
Melanoma Oncology and Immunology
Depositing User: General Admin
Identification Number: 10.3390/cancers14020323
ISSN: 2072-6694
Date Deposited: 17 Mar 2022 01:49

One of the limitations of immunotherapy is the development of a state referred to as T cell exhaustion (TEx) whereby T cells express inhibitory receptors (IRs) and lose production of effectors involved in killing of their targets. In the present studies we have used the repeated stimulation model with anti CD3 and anti CD28 to understand the factors involved in TEx development and treatments that may reduce changes of TEx. The results show that addition of nicotinamide (NAM) involved in energy supply to cells prevented the development of inhibitory receptors (IRs). This was particularly evident for the IRs CD39, TIM3, and to a lesser extent LAG3 and PD1 expression. NAM also prevented the inhibition of IL-2 and TNFα expression in TEx and induced differentiation of CD4+ and CD8 T cells to effector memory and terminal effector T cells. The present results showed that effects of NAM were linked to regulation of reactive oxygen species (ROS) consistent with previous studies implicating ROS in upregulation of TOX transcription factors that induce TEx. These effects of NAM in reducing changes of TEx and in increasing the differentiation of T cells to effector states appears to have important implications for the use of NAM supplements in immunotherapy against cancers and viral infections and require further exploration in vivo.

Alavi, Sara
Emran, Abdullah Al
Tseng, Hsin-Yi
Tiffen, Jessamy C.
McGuire, Helen Marie
Hersey, Peter
Last Modified: 17 Mar 2022 01:49

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