A team of researchers has identified a previously unknown mechanism that allows cancers to evade the bodyu2019s immune defenses, potentially opening a new chapter in cancer treatment. The discovery, published in the journal Nature, centers on a molecule called SLAMF6, found on the surface of immune cells, which acts as an internal brake that can weaken and exhaust the very T cells meant to destroy tumors.
The findings come from a team led by Dr. Andru00e9 Veillette, a professor of medicine at the Universitu00e9 de Montru00e9al and director of the Molecular Oncology Research Unit at the Montreal Clinical Research Institute. Unlike most known immune checkpoints, which require interaction with tumor cells to suppress immune responses, SLAMF6 can activate itself directly on the surface of T cells u2014 giving it a unique and stealthy ability to dampen the bodyu2019s cancer-fighting response from within.
How SLAMF6 Weakens the Immune System
When SLAMF6 binds to itself on the surface of T cells, it sends signals that produce three damaging effects: it reduces the ability of T cells to attack cancer cells, decreases the production of durable long-lasting immune cells, and accelerates a state known as immune exhaustion u2014 in which T cells gradually lose their effectiveness against tumors over time.
Many current cancer immunotherapies, including widely used PD1 and PDL1 inhibitors, work by removing inhibitory signals created by tumors. While these treatments have benefited millions of patients, a significant proportion either fail to respond initially or eventually develop resistance, leaving oncologists with limited options.
New Antibodies Offer a Solution
To counter SLAMF6, Veillette and his colleagues developed monoclonal antibodies designed to prevent the molecule from binding to itself and triggering its suppressive signals. Laboratory testing showed several promising results: increased activation of human T cells, larger numbers of durable immune cells, fewer exhausted T cells, and strong anti-tumor responses in mice.
u201cBy 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,u201d said Dr. Jean-Franu00e7ois Cu00f4tu00e9, president and scientific director of the IRCM.
The researchers say these newly developed antibodies perform significantly better than any existing approach aimed at targeting SLAMF6. The antibodies could be used on their own or combined with other immune-stimulating therapies, and may prove particularly valuable for patients who have stopped responding to PD1 or PDL1 treatments.
Path to Clinical Trials
The next step will be early-stage clinical trials to evaluate the safety and effectiveness of the treatment in people with solid tumors and blood cancers. The study, titled u201cSLAMF6 as a drug-targetable suppressor of T cell immunity against cancer,u201d was funded by the Canadian Institutes of Health Research, the Terry Fox Research Institute, BioCanRx, and the Canadian Foundation for Innovation.
If the approach proves safe and effective in human trials, it could form the basis of an entirely new class of cancer immunotherapies u2014 one that targets an internal brake no existing treatment has addressed.
Marcus Chen
Marcus Chen covers technology, AI, and digital infrastructure from Silicon Valley to Shenzhen.