Scientists have identified a previously unknown mechanism that may help cancer evade the immune system. The discovery focuses on SLAMF6, a molecule on the surface of immune cells that can prevent T cells from launching a powerful attack against tumors. In experiments using mice, the researchers also developed a way to block its activity.
The findings come from a team led by Dr. Andre Veillette, a professor of medicine at the University of Montreal and director of the Molecular Tumor Research Unit at the Institut Clinical Research de Montréal (IRCM), which is affiliated with UdeM. Their research was published in the journal nature.
Hidden immune system brakes
Researchers discovered that SLAMF6 works differently than many other molecules that suppress immune responses. Most known immune checkpoints require interaction with tumor cells to weaken the body’s defenses. However, SLAMF6 can be activated directly on the surface of T cells.
When this happens, a signal similar to the following is sent:
- Reduces the ability of T cells to attack cancer cells.
- Reduces production of strong, long-lasting T cells.
- A condition that accelerates immune depletion and causes T cells to lose their effectiveness against cancer.
Many current cancer immunotherapies, including PD1 and PDL1 inhibitors, work by removing inhibitory signals produced by tumors. Although these treatments have helped many patients, a significant number of patients do not respond or eventually develop resistance.
New antibodies boost cancer-fighting T cells
To overcome the effects of SLAMF6, Veillette and colleagues created a monoclonal antibody designed to block the molecule from binding to itself and triggering an inhibitory signal.
Laboratory tests showed some promising results, including:
- Increased activation of human T cells.
- More durable immune cells.
- Fewer T cells are exhausted.
- Strong antitumor response in mice.
According to the researchers, these newly developed antibodies perform significantly better than existing approaches targeting SLAMF6.
Potential new option for cancer patients
The research team believes this antibody could be the basis for a new type of cancer immunotherapy. These may be particularly useful for patients who no longer benefit from PD1 or PDL1 therapy.
Antibodies could potentially be used alone or in combination with other treatments designed to stimulate the immune system.
The next step is early-stage clinical trials to evaluate the safety and efficacy of the treatment for patients with solid tumors and blood cancers.
“The discoveries by Dr. Veillette’s team open the door to a new chapter in immunotherapy,” said Dr. Jean-François Côté, IRCM President and Scientific Director.
“By identifying a previously unrecognized internal brake and developing antibodies that can neutralize it, our researchers are providing an innovative solution to the limitations of current treatments,” he said.
“This groundbreaking advance, rooted in a strategic vision to develop precision treatments, brings real hope to many patients and is a powerful example of the impact of translational research conducted at IRCM.”
About research
The study “SLAMF6 as a drug-targeted suppressor of T cell immunity against cancer” by André Veillette et al. nature.
Funding for this study was provided by the Canadian Institutes of Health Research (CIHR), the Terry Fox Institute, BioCanRx, Quebec’s Ministry of Economy, Innovation and Energy, and the Canadian Foundation for Innovation.
