Harnessing T-Cell ‘Stemness’ Could Enhance Cancer Immunotherapy

A new study led by scientists at NCI sheds light on one way tumors may continue to grow despite the presence of cancer-killing immune cells. The findings, published Mar. 29 in Science, suggest a way to enhance the effectiveness of immunotherapies for cancer treatment.

Dying cancer cells release the chemical potassium, which can reach high levels in some tumors. The research team reported that elevated potassium causes T cells to maintain a stem-cell-like quality, or “stemness,” that is closely tied to their ability to eliminate cancer during immunotherapy. The findings suggest that increasing T cells’ exposure to potassium—or mimicking the effects of high potassium—could make cancer immunotherapies more effective.

“This study helps us better understand why cancer immunotherapy works the way it does,” said Dr. Nicholas Restifo, who led the research team. “It could also point the way toward generating better and more long-lasting responses to these treatments.”

Immunotherapy has led to remarkable results for some patients’ cancers, eradicating difficult-to-treat tumors and, in some cases, causing complete remission of disease. But many patients’ tumors do not respond to immunotherapy treatments and researchers are working to determine why this is.

In addition, some immunotherapy treatments, such as CAR T cells and immune checkpoint inhibitors, are limited by the lifespan of T cells. Cancer-fighting T cells inside the tumor can get “exhausted” and die. Therefore, researchers are exploring ways to help T cells used for immunotherapy not only last longer but also replicate and grow.