A research team led by Université de Montréal immunologist André Veillette reports that the immune receptor SLAMF6 can inhibit T cells by activating through interactions on the T cell surface itself, a mechanism the authors say could help explain why some patients fail to respond—or later stop responding—to checkpoint-based cancer immunotherapies. In the same study, the researchers describe monoclonal antibodies designed to block SLAMF6’s self-interaction, which boosted T-cell activity in laboratory tests and strengthened anti-tumor responses in mouse experiments.
Scientists led by Dr. André Veillette, a medical professor at the Université de Montréal and a director at the UdeM-affiliated Montreal Clinical Research Institute (IRCM), have identified SLAMF6 as an inhibitory molecule that can restrain T-cell anti-tumor activity.## A checkpoint-like mechanism that does not require tumor-cell contactIn laboratory experiments, the team found that SLAMF6 can inhibit T cells without needing to bind to a molecule on a tumor cell. Instead, it can activate through SLAMF6–SLAMF6 interactions on the T-cell surface, sending signals that weaken tumor-killing function, reduce the production of robust long-lived T cells, and accelerate T-cell exhaustion—an immune state in which T cells become less effective.The findings were reported in Nature in a paper titled “SLAMF6 as a drug-targetable suppressor of T cell immunity against cancer.”## Antibodies that block SLAMF6 self-interactionTo counter the inhibitory signal, the researchers developed monoclonal antibodies designed to block SLAMF6–SLAMF6 interactions. In experiments using human T cells, the antibodies increased activation and were associated with higher numbers of resilient, long-lasting T cells and fewer exhausted T cells. In mouse models, the approach was linked to stronger anti-tumor immune responses.## Next steps and fundingThe researchers said they aim to move next into early-phase clinical trials to evaluate safety and efficacy in people with solid tumors or blood cancers.The work reported in Nature lists support from multiple funders, including the Canadian Institutes of Health Research and the Terry Fox Research Institute, along with Québec’s Ministry of Economy and Innovation and BioCanRx.
