Discovery

McGill and Mount Sinai researchers identify PRMT7 as suppressor of CD8+ T cell expansion

Edited by Robert McTiernan··2 min read
McGill and Mount Sinai researchers identify PRMT7 as suppressor of CD8+ T cell expansion

A protein arginine methyltransferase acts as a previously unrecognized suppressor of cytotoxic T cell proliferation, offering a potential new target for improving cancer immunotherapy, according to a study published September 6 in Nature Communications by researchers at McGill University and the Icahn School of Medicine at Mount Sinai.

The work identifies protein arginine methyltransferase 7 (PRMT7) as a negative regulator of CD8+ T cell expansion through the nuclear factor kappa B (NF-κB) signaling pathway — the intracellular cascade that governs T cell activation, survival, and proliferation. When PRMT7 is absent or pharmacologically degraded, CD8+ T cells expand more robustly and mount stronger antitumor responses in preclinical models.

The study was led by corresponding authors Stéphane Richard at McGill's Segal Cancer Center and Lady Davis Institute for Medical Research, and Jian Jin at the Mount Sinai Center for Therapeutics Discovery. The Canada–US collaboration also included contributions from the Goodman Cancer Institute and the Structural Genomics Consortium at the University of Toronto, with additional involvement from the Centre Hospitalier de l'Université de Montréal (CHUM) and its affiliated research center.

Using genetic deletion and a targeted protein degrader — a proteolysis-targeting chimera (PROTAC) compound designated MS54 — the researchers found that removing PRMT7 enhanced CD8+ T cell proliferation in vitro and improved tumor control in a preclinical melanoma model. The mechanistic link to NF-κB is notable because this pathway sits upstream of multiple genes controlling T cell fate.

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Small-molecule inhibitors of PRMT7 have been reported, but targeted degraders can achieve more complete and sustained target elimination, which may be important for a protein whose relevant function does not depend on its catalytic activity and so cannot be addressed by enzymatic inhibition alone. The study does not describe IND-enabling studies or a clinical development program for MS54 or any related compound.

The broader PRMT family has attracted substantial drug development interest, most prominently through PRMT5 inhibitors such as GSK3326595, which GlaxoSmithKline advanced into Phase I development. PRMT7 is structurally and functionally distinct from PRMT5, however, making PRMT7-directed agents a separate therapeutic approach.

Whether the effect translates to tumor types beyond melanoma remains to be established. The study does not report data on T cell exhaustion or memory formation, both of which would be relevant to any clinical application in immuno-oncology.

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