Preventing exhaustion in immune cells boosts immunotherapy in mice
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PITTSBURGH, March 6, 2018 – If you’re an immune cell gearing up to fight cancer, you’d better eat your breakfast. The tumor microenvironment is a harsh place, and tumor cells are ready to wear you out.

Cancer immunotherapies that improve the ability of T-cells – highly specialized immune soldiers – to attack cancer have made major strides in the clinic. However, they work only for 10 to 30 percent of cancer patients. One reason for this is a phenomenon called “T-cell exhaustion,” where the T-cells that are most specialized to kill cancer are continually stimulated, becoming drained of their energy due to the harsh conditions inside the tumor. New research from the University of Pittsburgh School of Medicine and the UPMC Hillman Cancer Center shows that preventing or reversing this metabolic exhaustion with targeted therapies could enhance the effects of immunotherapy, potentially allowing them to help more patients.

The research, published today in the Journal of Experimental Medicine, reveals this insight by uncovering how a protein on the surface of T-cells, called 41BB, works. 41BB is part of a family of “co-stimulators” normally activated when T-cells are fighting infections, but the conditions inside a tumor prevent this from occurring.

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