How cancer cells escape immunotherapy
About 20% of patients with the skin cancer Merkel cell carcinoma relapse after responding to a treatment that combines a checkpoint inhibitor with immune-boosting T cells that are taken from patients, grown in a lab and then infused back into the body. Scientists at the Fred Hutchinson Cancer Research Center believe they know why. By studying cancer cells from two patients who relapsed after initially responding to the treatment, they discovered that one piece of a trio of genes known as human leukocyte antigens (HLAs) was missing, which made the tumors invisible to the T cells. When they applied drugs that are already on the market to treat other cancers to the cells, the HLAs became functional again, allowing the T cells to recognize the cancer, they reported in the journal Nature Communications. They believe their findings can be used to treat relapses that occur after immunotherapy. (Release)
Unraveling the link between ApoE4 and dementia
The protein ApoE4 has been linked to the two most common forms of dementia, Alzheimer’s and vascular dementia, though its exact role is unclear. Researchers at Weill Cornell Medicine have discovered that ApoE4 reduces both the number and the responsiveness of blood vessels in the brain, they reported in Nature Communications. In mice with ApoE4, they observed reduced blood flow while resting and an inability to boost that blood flow in response to brain activity. Mice with the more common ApoE3 variant had the same cerebral blood flow as normal mice did. ApoE4’s damaging effect on blood flow increases the risk of brain damage, they say, which could explain the amyloid plaques and tangles that are characteristic of Alzheimer’s disease. (Release)
Gut protein could make bone marrow transplants safer
Graft-versus-host disease (GVHD) is a dangerous complication of bone marrow transplants that occurs when immune cells in donated marrow attack the gastrointestinal tract. Now scientists at Mount Sinai have found that a protein called regenerating islet-derived 3-alpha, which is found in the gut, has antimicrobial properties that may protect against the reaction. In a study, they demonstrated that mice without the protein could not survive GVHD. But adding regenerating islet-derived 3-alpha to human gastrointestinal cell lines prolonged cell survival. They believe the protein could not only make bone marrow transplants safer, but it might also help treat immune diseases of the gastrointestinal tracts, such as inflammatory bowel disease. (Release)