Studies show that T-cell metabolism, anti-tumor immune response to protein is important

Studies show that T-cell metabolism, anti-tumor immune response to protein is important

WASHINGTON: Researchers at the University of Texas MD Anderson Cancer Center have discovered that a protein called NF-kappa B-inducing kinase (NIK) is essential for changes in metabolic activity associated with T cell activation. This regularly becomes an important factor. Anti-tumor immune response.
The fact published today in Nature Immunology suggests that increasing NIK activity in T cells may prove to be a promising strategy to increase the effectiveness of immunotherapy, including adopting cellular therapy and immune checkpoints. Includes layout.
In a realistic melanoma model, researchers evaluated engineered melanoma-related T cells to express high levels of NIK. Compared to control, these T cells demonstrated improved tumor-killing abilities and survival, suggesting that NIK activity may improve the effectiveness of increased T cell therapies.
“NIK is a new regulator of T cell metabolism that works in a very unique way. Biologically, the activity of NIK stabilizes the HK2 glycolytic enzyme by regulating the cellular redox pathway.” Immunology.
Sun added, “From a therapeutic point of view, we have been able to improve the efficacy of T cell therapies adopted in the clinical model by over-performing NIK in these cells.”
Sunday said that T cells are generally in a relatively quiet state with low energy demand and very low cell count. However, upon antigen recognition, T cells begin to expand and activate the glycosylated metabolic pathway to meet the increasing energy requirements of their immune function.
This metabolic shift is controlled by immune check proteins, such as CTLA-4 and PD-1, which work to suppress T cell metabolism. In this way, T cells can boost anti-tumor activity by boosting immune metabolism.
In addition, when T cells are activated, they begin to produce proteins called costimulatory molecules, which work to stimulate metabolism and immunity.
Knowing that the NIK protein acts on the flow of many of these costimulatory molecules, the researchers sought to better understand its role in regulating T cell function.
In the melanoma model, NI damage increases tumor load and decreases tumor-infiltrated T cells, suggesting that NIT plays an important role in anti-tumor immunity and T cell survival. Is.
Further experiments have shown that NI is essential for metabolic reprogramming in activated T cells through the cellular redox system’s own control. Increased metabolism can lead to elevated levels of the oxygen species (ROS), which can damage cells and trigger protein degradation.
The researchers found that NIK maintains the NADPH redox system, an important antioxidant mechanism for reducing ROS accumulation. This results in the stabilization of the HK2 protein, which is a rate-limiting enzyme in the path of glycolysis.
“Our research shows that without NIK, the HK2 protein is not stable, and it is being rejected. You need NIK to maintain HK2 levels in T cells. Interestingly, we have learned that by adding more NIK to cells, you can increase levels further, said HK2 and activate glycolysis.
As a potential therapeutic treatment, researchers are currently working to test modified Chimeric Antigen Receptor (CAR) T cells in a laboratory engineered by an experienced NIK.
In the future, they hope to find other treatments, such as target therapies that can combine NIK activity with other immunotherapy modalities, including immune blockers.

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