Researchers from China and the United States have identified a mechanism that explains why the body’s main defense cells against cancer end up “tiring” and stopping working. The discovery, published in two international scientific journals on January 14, 2026, points to a possibility to reactivate these cells and increase the effectiveness of treatments such as immunotherapy and CAR-T cell therapies.
CD8+ T cells are known as the “soldiers” of the immune system. They recognize and attack tumor cells. The problem is that, when they are exposed to cancer for a long time, they enter a state called exhaustion, in which they lose strength, energy and ability to fight the tumor. The study shows that this process happens because of a “domino effect” within the cell itself.
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The research was led by Li Guideng, from the Suzhou Institute of Systems Medicine, in China, in partnership with Philip D. Greenberg, from the Fred Hutchinson Cancer Center, in the United States. Scientists discovered that the constant stimulation caused by the tumor activates an internal mechanism that turns off a protein called FOXO1.
Under normal conditions, FOXO1 functions as a “coordinator” that keeps the cell healthy, active and with memory capacity. When FOXO1 is blocked, the cell stops producing an essential enzyme called KLHL6.
KLHL6 works as a kind of “cleaner”. It marks harmful proteins so that they are destroyed. Among these proteins are:
- TOX, which accelerates the cell exhaustion process;
- PGAM5, which harms mitochondria — the cell’s “power plants.”
Without enough KLHL6, these proteins accumulate, causing the cell to lose energy and become permanently exhausted. It’s like a soldier who, in addition to being unmotivated, runs out of fuel to continue fighting. In this case, according to the researchers, by artificially increasing the levels of KLHL6, the T cells regained energy and the ability to fight the tumor.
T cell exhaustion is one of the main challenges of immunotherapy, a treatment that stimulates the patient’s own immune system to attack the cancer. Today, some therapies work well at first, but may lose their effect when the cells enter this state of “terminal fatigue”. Understanding what causes this blockage helps you think of new solutions.
According to scientists, increasing the activity of KLHL6 or mimicking its function could prevent T cells from running out. This could make existing treatments, such as immune checkpoint blockade and CAR-T and TCR-T cell therapies, more long-lasting and potent.
Giovanna Sfalsin
Reporter
Journalism student at Centro Universitário IESB, with experience in the Cities editorship of Correio Braziliense and in press relations. Currently, CB-Online reporter
date:2026-02-10 20:01:00