Researchers have uncovered a molecular mechanism that allows tumors to suppress the immune system in ways previously unknown to medicine. The discovery offers a potential new weapon for cancer patients whose bodies have stopped responding to existing treatments.
The culprit is a molecule called SLAMF6, which sits on the surface of immune cells and quietly tells T cells to stand down in their fight against cancer. Unlike most immune checkpoints studied to date, SLAMF6 doesn't require tumor cells to activate it. It can trigger its suppressive signals all on its own, working as what researchers describe as an internal brake on the immune response.
Dr. André Veillette's team at Montreal's IRCM identified what happens when SLAMF6 becomes active. It weakens T cells' ability to attack tumors, reduces the formation of long-lasting immune cells, and accelerates immune exhaustion, a condition where T cells essentially give up the fight. The findings were published in Nature.
The discovery matters because current cancer immunotherapies like PD1 and PDL1 inhibitors have stalled for many patients. Some never respond to these drugs in the first place. Others initially benefit, then develop resistance. If SLAMF6 is part of the reason why, blocking it could reopen doors that appeared closed.
Veillette's team developed monoclonal antibodies designed to stop SLAMF6 from activating itself. In laboratory tests, the antibodies produced measurable improvements: they increased T cell activation, boosted the numbers of durable immune cells, reduced exhausted T cells, and triggered strong anti-tumor responses in mice. The researchers say their new antibodies outperform any existing approach aimed at targeting SLAMF6.
The hope is that these antibodies could form the basis of a new class of cancer immunotherapies. They might work alone or be combined with other immune-stimulating treatments. Researchers are particularly interested in testing them on patients who no longer benefit from existing checkpoint inhibitors.
The next phase involves early stage clinical trials in people with solid tumors and blood cancers. The work was funded by the Canadian Institutes of Health Research, the Terry Fox Research Institute, and other Canadian health and innovation agencies.
Author Jessica Williams: "Finding an immune brake that's been invisible to researchers until now, then immediately developing a way to release it, is exactly the kind of discovery that breaks through treatment resistance."
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