A significant advancement has been achieved by cancer immunotherapy researchers, who have identified SLAMF6, a surface molecule on immune cells that impedes the efficacy of T cell tumor assault. Promisingly, a method to neutralize this molecule has been successfully demonstrated in murine models.
This groundbreaking work, spearheaded by Dr. André Veillette, a distinguished medical professor at Université de Montréal and the director of the molecular oncology research unit at the affiliated Montreal Clinical Research Institute (IRCM), is documented in a recent publication in the esteemed journal, Nature.
An Intrinsic Regulator Independent of Tumor Cell Interaction
Within their laboratory investigations, Dr. Veillette’s team established that, in contrast to other inhibitory molecules, SLAMF6 does not necessitate engagement with tumor cells to diminish the immune response. Instead, it undergoes autoinactivation directly on the surface of T cells, initiating a signal that:
- Diminishes their offensive capabilities;
- Curbs the generation of resilient and enduring T cells;
- And hastens immune senescence, a condition where T cells become incapable of mounting an effective defense against malignancies.
Contemporary immunotherapeutic strategies, such as those employing PD1 or PDL1 inhibitors, function by disengaging the impediments that tumors impose on the immune system. However, a considerable proportion of patients exhibit a lack of responsiveness or eventually cease to benefit from these therapeutic interventions.
To surmount this challenge, Dr. Veillette and his collaborators engineered novel monoclonal antibodies designed to preclude SLAMF6 from self-interaction. These antibodies have exhibited noteworthy outcomes, including:
- Enhanced activation of human T cells;
- An increased population of robust immune cells;
- A reduction in the prevalence of senescent T cells;
- And potent antitumor responses observed in animal studies.
Surpassing Existing Therapeutic Modalities
According to Dr. Veillette and his fellow researchers, these novel antibodies demonstrably outperform all existing agents targeting SLAMF6, positioning them as frontrunners for the next generation of anticancer immunotherapies.
The potential utility of these antibodies extends to patients who are no longer responsive to PD1 or PDL1 therapies. Furthermore, they could be administered as monotherapy or in conjunction with complementary immune-boosting treatments, as indicated by the research team.
Moving forward, Dr. Veillette’s group intends to initiate early-phase clinical investigations to assess the safety profile and therapeutic effectiveness of these antibodies in individuals diagnosed with solid tumors or hematological cancers.
The discovery by Dr. Veillette’s research group heralds a new epoch in the field of immunotherapy.”
Dr. Jean-François Côté, President and Scientific Director of the IRCM
“By pinpointing an internal inhibitory mechanism that remained undetected until now and by developing antibodies capable of its neutralization, our researchers are providing an innovative resolution to the inherent limitations of current therapeutic approaches,” he commented.
“This breakthrough, grounded in a strategic objective to advance precision therapeutics, offers substantial optimism for numerous patients and exemplifies the significant impact of the translational research conducted at the IRCM.”
University of Montreal
Li, B., et al. (2026). SLAMF6 as a drug-targetable suppressor of T cell immunity against cancer. Nature. DOI: 10.1038/s41586-026-10106-5. https://www.nature.com/articles/s41586-026-10106-5
