Researchers have uncovered a previously hidden “internal brake” on immune cells that limits their ability to fight cancer, independent of tumor influence.
Scientists developing next-generation cancer immunotherapies have uncovered a hidden weakness inside the immune system itself. A molecule known as SLAMF6, found on T cells, acts as a built-in shutoff switch that limits their ability to destroy tumors. In experiments with mice, researchers were able to block this signal, effectively restoring the cells’ cancer-fighting power.
The discovery, led by Dr. André Veillette of Université de Montréal at the Montreal Clinical Research Institute (IRCM), appears in Nature and highlights a form of immune suppression that operates independently of tumors.
An internal brake independent of tumor cells
Veillette’s team found that SLAMF6 acts differently from other inhibitory molecules. It does not need to interact with tumor cells to suppress the immune response. It self-activates directly on the surface of T cells, sending a stop signal that:
- weakens their attack capacity;
- reduces the production of healthy, robust, long-lasting T cells;
- and accelerates immune exhaustion, a state in which T cells become ineffective against cancer.
Existing immunotherapies, including PD1 and PDL1 inhibitors, work by removing external “brakes” imposed by tumors. However, many patients either do not respond or eventually stop responding to these treatments.
To counter this effect, Veillette and his co-researchers developed new monoclonal antibodies that prevent SLAMF6 from interacting with itself. These antibodies have shown remarkable effects that include:
- more activation of human T cells;
- higher numbers of resilient immune cells;
- fewer exhausted T-cells;
- and strong anti-tumor responses in mice.
Outperform all other approaches
According to the researchers, these antibodies outperform all existing strategies aimed at SLAMF6, making them promising candidates for a new class of cancer immunotherapies.
They may provide an option for patients who no longer benefit from PD1 or PDL1 inhibitors and could be used either on their own or alongside other immune-based treatments.
The next step is to evaluate safety and effectiveness in early-phase clinical trials involving patients with solid tumors or blood cancers.
“The discovery made by Dr. Veillette’s team opens the door to a new chapter in immunotherapy,” said IRCM president and scientific director Dr. Jean-François Côté.
“By identifying an internal brake that had until now gone unrecognized and by developing antibodies capable of neutralizing it, our researchers are offering an innovative solution to the limitations of current treatments,” he said.
“Rooted in a strategic vision to develop precision therapeutics, this breakthrough brings real hope to many patients and stands as a strong example of the impact of the translational research conducted at the IRCM.”
Reference: “SLAMF6 as a drug-targetable suppressor of T cell immunity against cancer” by Bin Li, Ming-Chao Zhong, Cristian Camilo Galindo, Jiayu Dou, Jin Qian, Zhenghai Tang, Dominique Davidson and André Veillette, 11 February 2026, Nature.
DOI: 10.1038/s41586-026-10106-5
Funding was provided by the Canadian Institutes of Health Research (CIHR), the Terry Fox Research Institute, BioCanRx, Québec’s Ministry of Economy, Innovation and Energy, and the Canadian Foundation for Innovation.
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2 Comments
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This excellent research can improve immunotherapy treatments and save many lives.