-
Categories
-
Pharmaceutical Intermediates
-
Active Pharmaceutical Ingredients
-
Food Additives
- Industrial Coatings
- Agrochemicals
- Dyes and Pigments
- Surfactant
- Flavors and Fragrances
- Chemical Reagents
- Catalyst and Auxiliary
- Natural Products
- Inorganic Chemistry
-
Organic Chemistry
-
Biochemical Engineering
- Analytical Chemistry
-
Cosmetic Ingredient
- Water Treatment Chemical
-
Pharmaceutical Intermediates
Promotion
ECHEMI Mall
Wholesale
Weekly Price
Exhibition
News
-
Trade Service
Cancer is an important factor endangering human health
.
Immunotherapy, including CAR-T cell therapy and immune checkpoint blockade, is an effective clinical cancer treatment; however, the beneficiary population of these immunotherapies is still limited
Nicotinamide adenine dinucleotide (NAD+) is a coenzyme in redox reactions, which can directly and indirectly affect key cellular functions such as cellular metabolic pathways, DNA repair, chromatin remodeling, and cellular senescence
.
On August 10, 2021, Professor Gao Feng Fan and Professor Haopeng Wang from the School of Life Science and Technology, ShanghaiTech University, as co-corresponding authors, published an online article in the journal Cell Reportsentitled: NAD+ supplement potentiates tumor-killing function by rescuing defective TUB-mediated NAMPT Research paper on transcription in tumor-infiltrated T cells
.
This study shows that NAD+ levels enhance the effect of tumor immunotherapy, and elucidates the TUBBY-NAMPT-NAD+ regulation signaling pathway in tumor-infiltrating T cells
.
This study found that the NAD+ salvage pathway mediated by nicotinamide phosphoribosyltransferase (NAMPT) is required for T cell activation through genome-wide CRISPR screening experiments and high-throughput metabolic inhibitor screening experiments
.
In addition, further analysis of NAD+ levels in peripheral blood T cells and tumor-infiltrating T cells (TILs) showed that NAD+ levels in TILs were relatively low
Further screening demonstrated that the expression level of NAMPT is dynamically controlled by the transcription factor Tubby, and the activity of Tubby is dependent on the TCR-PLCg signaling axis
.
To investigate how reduced NAD+ levels affect T cell activation, the authors found through LC-MS and isotope labeling experiments that too low NAD+ levels in T cells would lead to inhibition of the glycolytic pathway and disruption of mitochondrial function, thereby blocking the ATP synthesis and TCR cascade signaling
Finally, the paper further verified in the anti-CD19 CAR-T treatment model and the anti-PD-1 immune checkpoint inhibitor treatment model that NAD+ supplementation significantly enhanced the tumor-killing effect of T cells
.
The researchers found that in the anti-CD19 CAR-T treatment model, almost all mice in the CAR-T treatment group supplemented with NAD+ achieved tumor clearance, while only about 20 mice in the CAR-T treatment group without NAD+ supplementation.
% of mice achieved tumor clearance
.
Consistent with this, in the anti-PD-1 immune checkpoint inhibitor treatment model, B16F10 tumors were relatively resistant to anti-PD-1 treatment, and the inhibitory effect was not significant; however, the combination of anti-PD-1 and NAD+ B16F10 tumor growth in the treatment group could be significantly inhibited
The authors believe that the combined use of NAD + food supplements can significantly enhance T cell activation, which is expected to affect cancer immunotherapy regimens and provide possible new strategies for tumors with poor immunotherapy effects
.
At present, they mainly conduct related research in animal tumor models
Assistant Researcher Wang Yuetong, Ph.
Original source:
Original source:Yuetong Wang, et al.
NAD+ supplement potentiates tumor-killing function by rescuing defective TUB-mediated NAMPT transcription in tumor-infiltrated T cells Leave a Comment
