Scientists at UC San Francisco discovered a new method for controlling the natural killer cells in the immune system through tissue implants and cell therapies that can enhance immunotherapies’ ability to detect/destroy cancerous tumors.
A major challenge with regenerative medicine is the immune system’s ability to reject implanted tissues recognized as non-self. Immunological rejection is a significant obstacle that stunts success in stem cell transplantation. Overcoming immune rejection of transplanted stem cells can support the development of off-the-shelf immunotherapies that can be used in any patient.
Scientists at the University of California, San Francisco, Department of Surgery’s Transplant and Stem Cell Immunobiology Laboratory study how to produce cells and tissues that can be transplanted without being subjected to immune system rejection. The approach is accomplished via molecular engineering of cells that essentially trigger immune checkpoints. Checkpoints, when activated, stop immune cells from attacking the body’s own cells. Cancer cells can use this strategy to evade immune cell attack by expressing CD47, a protein that activates the signal-regulatory protein alpha (SIRP-alpha) switch on immune cells.
Although it was expected to evade the T-cell attack of the engineered hyperimmune stem cells, the cells were surprisingly able to evade natural killer (NK) cell attack. It was thought that NK cells do not express the SIRP-alpha checkpoint. The researchers found that the stem cells overexpressing CD47 can turn off NK cells via the SIRP-alpha checkpoint. The lack of checkpoints were in immortalized NK cell lines, but the checkpoint detected in the study were in NK cells taken directly from patients and from an inflammatory environment, and thus activated by cytokines.
The implanted cells behave as if “invisible” to the immune system. The finding that engineered stem cells can shut down NK cell attack opens the door for a novel approach to develop cancer immunotherapies. Immune cells that can specifically recognize and attack tumors would be able to do so without the risk of rejection of the injected cells. There is the potential to develop off-the-shelf cell therapies that can be used safely and effectively in any patient. Such treatments can be more rapidly accessible and applied while being more cost-effective than currently available immunotherapies.
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Scientists Discover a Way to Control the Immune System’s “Natural Killer” Cells With “Invisible” Stem Cells. (2021). Retrieved 12 February 2021, from https://scitechdaily.com/scientists-discover-a-way-to-control-the-immune-systems-natural-killer-cells-with-invisible-stem-cells/