Immunotherapy has transformed cancer treatment over the past decade, but it does not work for everyone. Many patients never respond, and others who initially benefit eventually relapse. A team at the University of Montreal may have found the reason why.
The culprit is a molecule called SLAMF6, found on the surface of T cells — the immune system's frontline soldiers. Normally, SLAMF6 acts as a self-regulatory brake, preventing T cells from becoming overactive and attacking healthy tissue. But in the context of cancer, this brake works against the patient: tumors exploit it to keep T cells in check, blunting the immune attack.
The discovery, published in Nature, reveals that SLAMF6 operates independently of the well-known PD-1 pathway — the target of blockbuster drugs like Keytruda and Opdivo. This means that even when PD-1 is successfully blocked, SLAMF6 can still suppress T cell activity, explaining why many patients fail to respond to existing immunotherapies.
The researchers designed custom antibodies that bind to SLAMF6 and disable its braking function. In mouse models of cancer, this approach produced superior anti-tumor activity compared to PD-1 blockade alone. When both brakes were released simultaneously, the immune response was even more powerful.
For patients whose cancers have stopped responding to current treatments, this represents a genuine new hope. Clinical trials in humans would be the next step, and the researchers are already working toward that goal. The finding also suggests that future cancer therapy may need to engage multiple immune checkpoints simultaneously rather than relying on a single target.
Knowledge takeaway: University of Montreal researchers identified SLAMF6 as a hidden immune brake on T cells that helps cancers resist immunotherapy; custom antibodies that neutralize SLAMF6 showed superior results in mice, offering a new treatment pathway for patients whose current therapies have stopped working.