| Health / Health News |
Harnessing T-cell “stemness” could enhance cancer immunotherapy
A new study led by scientists in the Center for Cancer Research (CCR) at the National Cancer Institute (NCI) sheds light on one way tumors may continue to grow despite the presence of cancer-killing immune cells.
Killer T cells surround a cancer cell “the kiss of death”. Photo: Alex Ritter, Jennifer Lippincott Schwartz, Gillian Griffiths/NIH
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 life span 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 replicate and grow.
The team established that high levels of potassium inside tumors released by dying cancer cells can shut off cancer-killing T cells that have invaded the tumor. In the new study, the researchers showed that growing T cells under conditions of high potassium also preserves the “stemness” of the T cells.
This means that, in the tumor, the stem-cell-like T cells have the ability to replicate themselves, but they aren’t able to mature into killer immune cells. By keeping T cells in this state, the tumors can avoid attack and continue to grow. This could explain how a cancer could grow despite the presence of T cells that would seemingly be able to fight the cancer.
However, when the stem-cell-like T cells are removed from the tumor, grown to large numbers in the lab, and then returned to the patient — as they are in a primary immunotherapy strategy called adoptive cell transfer — the stem-cell-like T cells can mature into killer cells that can attack the tumor.
The preserved stemness of T cells — that is, their ability to self-renew indefinitely and respond to stimulation to become cancer-fighting cells — may be what allows adoptive cell transfer therapy to be successful.
The researchers explored preserving T cells’ stemness with high potassium levels for therapeutic use. T cells grown in the presence of extra potassium and transplanted into mice shrank primary and metastatic melanoma tumors better than T cells grown in normal levels of potassium.
When exposed to a high concentration of potassium, both T cells isolated from patient tumors as well as genetically engineered anticancer T cells had higher levels of markers associated with continued growth and improved immunotherapy outcomes.
The research team demonstrated that when they used specific drugs to mimic potassium’s effects on T cells in mice, this improved the T cells’ ability to continue to grow and eliminate tumors. This means that such a drug could potentially be used to induce stemness in T cells as a strategy to enhance cancer immunotherapies. (National Institutes of Health)
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