Biochemical controls: T cell controls (Introduction)

by David Turell , Saturday, May 04, 2024, 20:58 (201 days ago) @ David Turell

Activated (HK) T cells:

https://www.sciencedaily.com/releases/2024/05/240503172616.htm

"Activated T cells that carry a certain marker protein on their surface are controlled by natural killer (NK) cells, another cell type of the immune system. In this way, the body presumably curbs destructive immune reactions. Researchers from the German Cancer Research Center (DKFZ) and the University Medical Center Mannheim (UMM) now discovered that NK cells can impair the effect of cancer therapies with immune checkpoint inhibitors (ICI) in this way. They could also be responsible for the rapid decline of therapeutic CAR-T cells. Interventions in this mechanism could potentially improve the efficacy of these cellular cancer immunotherapies.

"The T cells of the immune system are the main players in the defense against viral infections and tumor cells. On the other hand, they attack the body's own healthy tissue in autoimmune reactions, which can even be fatal. The body must therefore keep a tight control on T cell activity.

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"'Studies have shown that NK cells can also kill activated T cells and thus limit their proliferation," says Michael Platten, Head of Department at the DKFZ and Director of the Neurological University Clinic Mannheim. "However, until now we did not know which feature characterizes T cells as a target for the NK cell."

"When screening activated T cells from healthy donors, Platten's team identified the protein B7H6 as a recognition molecule for NK cell attacks in a new study. Activated T cells from the blood of patients with autoimmune diseases, cancer or viral infections expose large amounts of B7H6 on their surface. Co-culture experiments in the culture dish showed that NK cells recognize the activated T cells by their B7H6 expression. In contrast, T cells whose B7H6 gene was destroyed with the CRISPR-Cas were protected from the lethal attack of the NK cells.

"'The elimination of T cells by NK cells is triggered by an intrinsic mechanism of the T cells. The activated T cells temporarily identify themselves as targets for NK-induced cell lysis," explains Michael Kilian, first author of the publication, and adds: "This may limit excessive activation and expansion of T cells as a control mechanism to curb destructive immune responses."

"'We now know a number of so-called checkpoint molecules that reduce or enhance the activation of T cells and thus modulate the course of immune reactions. B7H6 can now be classified as a further inhibitory immune checkpoint on T cells," explains study leader Platten.

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"'NK control of T cells has the potential to interfere with various forms of cancer immunotherapy. By specifically intervening in this process, it may be possible to modulate T cell immune responses in the future," explains Michael Platten, head of the current study. With the help of the CRISPR-Cas gene scissors, the researchers now want to protect CAR-T cells from elimination by NK cells in a clinical trial together with the Department of Haematology and Oncology at Heidelberg University Hospital and thus improve the effectiveness of cellular immunotherapy."

comment: this degree of complex controls must be a designed process. Our human controls are now at a level of using CRISPR tailoring of DNA.