Most of the molecules that dampen the immune system need a tumor cell to do it. SLAMF6 does not. It sits on the surface of T cells and switches itself on, which is the odd feature that a Montreal team says explains part of why cancer drugs sometimes stop working.
The group is led by Dr. André Veillette, a medical professor at the Université de Montréal and director of the Molecular Oncology Research Unit at the Montreal Clinical Research Institute (IRCM). Their paper, “SLAMF6 as a drug-targetable suppressor of T cell immunity against cancer,” appeared in Nature.
A brake the tumor does not have to press
Once SLAMF6 activates itself, it sends signals that blunt the T cells’ ability to attack cancer cells. It also cuts the output of strong, long-lasting T cells and hastens immune exhaustion, the state in which T cells lose their punch against the disease.
That matters because of how current immunotherapy works. PD1 and PDL1 inhibitors strip away inhibitory signals that tumors create. Many patients have gained from them. A significant number, though, either never respond or become resistant after a time. A brake that fires without any help from the tumor would not be touched by a drug aimed at tumor-made signals.
Antibodies tested in mice
Veillette and colleagues built monoclonal antibodies that stop SLAMF6 from binding to itself, and so from setting off its suppressive signals. In experiments on mice, the antibodies kept immune cells stronger and let them go after tumors more effectively. The researchers said the antibodies perform significantly better than any earlier approach to targeting SLAMF6.
The team thinks the antibodies could anchor a new class of immunotherapies, with patients who no longer benefit from PD1 or PDL1 treatment the likeliest candidates. They might be given alone or alongside other drugs that stimulate the immune system.
Human testing is the next stage. Early-stage clinical trials are planned to check safety and effectiveness in people with solid tumors and blood cancers.
“The discovery made by Dr. Veillette’s team opens the door to a new chapter in immunotherapy,” said Dr. Jean-François Côté, IRCM president and scientific director. He called SLAMF6 “an internal brake that had until now gone unrecognized” and said the antibodies offer “an innovative solution to the limitations of current treatments.”
Funding came from the Canadian Institutes of Health Research, the Terry Fox Research Institute, BioCanRx, Québec’s Ministry of Economy, Innovation and Energy, and the Canadian Foundation for Innovation.
A separate line of attack in San Diego
Elsewhere, researchers at the University of California San Diego have been chasing the same problem from a different direction. A team led by Tariq Rana, chair of the Department of Cellular and Molecular Medicine at UC San Diego School of Medicine, looked at a small RNA molecule called microRNA-25. In several mouse cancer models, blocking it did little to tumor growth by itself but greatly improved the tumors’ response to immunotherapy.
The work, published on May 20, 2026, in Nature Communications, traced the effect to a protein called Syndecan-3. The authors suggest the miR-25 and SDC3 pathway could one day help turn immunotherapy-resistant “cold” tumors into “hot” ones that respond to treatment.
Both studies are preclinical. Anyone with questions about their own treatment should speak to their doctor.
Sources
- The secret reason some cancer treatments stop working
- UC San Diego Study Uncovers Molecular “Shield” Behind Cancer Immunotherapy Resistance
