Blocking One Signal Kept Cancer-Fighting T Cells From Burning Out in Lab Studies
Memorial Sloan Kettering researchers found that the signaling molecule MEK drives cancer-fighting T cells into exhaustion. Blocking it in animal and lab studies helped the cells conserve energy and last longer.
Researchers at Memorial Sloan Kettering Cancer Center have identified a signaling molecule, MEK, that pushes cancer-fighting T cells toward burnout, and found that blocking it helped the cells survive longer in animal and laboratory studies, according to the center. The work is published in the journal Immunity.
Exhausted T cells are overworked, not idle
Immunotherapy drugs such as checkpoint inhibitors unleash T cells against tumors, but the cells can wear out before the cancer is gone, a state called T cell exhaustion. The team found that exhausted cells were not sluggish at all. They were spending huge amounts of energy making cancer-killing proteins, and MEK controls how much of those proteins they make.
“A tragic part of T cell exhaustion is that the immunotherapy seems to be working for patients, and then it fades.” — Santosha Vardhana, MD, PhD, physician-scientist, Memorial Sloan Kettering Cancer Center
When the researchers treated T cells with MEK inhibitors, the cells multiplied more while using less energy and kept working in the hostile environment around tumors. First author Tanmana Mitra, a student in Vardhana’s lab, said it changed the view of exhaustion “from a problem of too little energy to one of excessive energy demand.”
The approach involves a trade-off
Blocking MEK makes the immune attack less intense but longer-lasting, so it is unlikely to suit every patient, the researchers caution. They suggest it may help those who respond poorly to standard immunotherapy, such as people with large tumors or few cancer-recognizing immune cells. The findings come from animal and lab models and have not yet been tested in patients.
Because MEK inhibitors are already FDA-approved for other uses, Vardhana said the idea “could be tested in humans without much delay.” The study’s full details are in Immunity.
It adds to other work on harnessing T cells against disease, including CAR T-cell therapy for severe rheumatoid arthritis.
Like what you're reading?
Related stories
Blood Markers Can Flag Lung Cancer Risk Up to 10 Years Early, Study Finds
University of Hawaiʻi researchers identified 31 blood markers linked to future lung cancer risk that can be detected up to a decade before diagnosis, with 95% accuracy in their computer model.
Enzyme Shields Mouse Livers From Fat, Inflammation and Scarring, Study Finds
Researchers co-led by Cedars-Sinai found that the enzyme UBE2N declines as fatty liver disease worsens, and that restoring it in mice reduced fat buildup, inflammation and scarring. The work is preclinical.
High-Dose Vitamin B3 Shows Early Promise Against Glioblastoma in Small Calgary Trial
In an interim analysis of a University of Calgary trial, 82% of 24 glioblastoma patients given controlled-release niacin alongside standard treatment had no cancer progression after six months. The researchers stress the results are preliminary.
