In a discovery that could expand the array of current cancer immunotherapy treatments, scientists at Harvard Medical School have identified a new molecular brake that hinders the ability of T cells to attack tumors.
- By EKATERINA PESHEVA
The research, published Aug. 12 in Nature Immunology and supported in part by federal funding, offers a new pathway to design treatments that help more patients - a welcome development given that current cancer immunotherapies work in less than half of those who receive them.
The research, done in mice and in human cells, shows that a protein called STUB1 restrains the immune system's elite cancer-fighting CD8+ T cells. It does so by interfering with immune-signaling receptors - particularly one for the molecule IL-27 - that are crucial for T cells' ability to mount a vigorous anti-tumor response.
Blocking STUB1, the researchers said, could lead to new ways to supercharge cancer immunotherapies.
"Even though cancer immunotherapies have transformed the way we treat cancer, it's important that we find new ways to extend the lifesaving and lifechanging benefits of these therapies to more people," said lead author Martin LaFleur, a postdoctoral researcher in the lab of Arlene Sharpe, the Kolokotrones University Professor in the Blavatnik Institute at HMS, a pioneer in cancer immunotherapy, and senior author on the work. "We believe our work and CRISPR screens more broadly are critical for identifying and prioritizing possible therapeutic targets to find the best ones for patients."
What the researchers found
Using the gene-editing tool CRISPR, the researchers screened nearly 900 genes to see which ones might be preventing the CD8+ T cells from attacking tumors effectively. One gene stood out: STUB1. When the researchers deleted this gene in CD8+ T cells, these cells became markedly better at attacking tumors. Mice with STUB1-deficient T cells had slower-growing cancers and lived longer than those with unaltered T cells.
