Targeting Inhibitory Proteins Strengthened NK Cell Cancer Killing Across Tumor Types

Scientists have developed a strategy to boost the cancer-fighting power of natural killer (NK) cells, part of the immune system’s first line of defence. NK cells can detect and destroy cancer cells, but tumours often create a protective barrier that blocks them, allowing cancer to grow.

Researchers at McGill University’s Rosalind & Morris Goodman Cancer Institute, in collaboration with the Research Institute of the McGill University Health Centre, found that suppressing two specific proteins helps NK cells overcome this blockage, turning them into more potent cancer killers.

In preclinical experiments, the approach effectively killed human cancer cells across several hard-to-treat tumour types – including leukemia, glioblastoma, kidney cancer and triple-negative breast cancer – and significantly slowed tumour growth in animal models.

“This approach is particularly promising for patients who currently have very few options, when standard treatments have failed,” said senior author Michel L. Tremblay, Distinguished James McGill Professor in McGill’s Department of Biochemistry and researcher at the Rosalind & Morris Goodman Cancer Institute.

A safer, scalable approach

Genetic editing, commonly used in cancer immunotherapies, permanently alters cells, increasing the risk of unintended side effects. The new approach instead uses small-molecule drugs to temporarily boost NK cell activity without making permanent changes that are harder to control.

Researchers say the treatment strategy could also overcome practical barriers that have limited the widespread use of cell-based therapies.

NK cells from umbilical cord blood donations, isolated at the Cellular Therapy Laboratory led by Pierre Laneuville and Linda Peltier at the Research Institute of McGill University Health Centre, were cultured and banked for the treatment of multiple patients. Unlike many current immunotherapies, which must be custom-built from each patient’s own cells, a process that can take weeks, these NK cells can be ready to use immediately.

“This approach will make immunotherapy at McGill University Health Centre faster, safer and more affordable,” added Chu-Han Feng, a research scientist at the Rosalind & Morris Goodman Cancer Institute. “It avoids the complex process of customizing cells and uses readily available drugs to reversibly enhance NK cells’ anti-tumour activities”.

Acute myeloid leukemia, an aggressive blood cancer, is among the first cancers the team hopes to target in future clinical trials, currently awaiting funding and regulatory approval.

Reference: Feng CH, Peltier L, Chouleur T, et al. PTPN1/PTPN2 inhibition improves NK cancer therapy by enhancing IL-2 and mitigating TGFβ1 responses. EMBO Rep. 2026. doi: 10.1038/s44319-026-00745-0

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