Some tumors – known as “cold tumors” – do not respond well to checkpoint inhibitors. To find out why, researchers from Brigham and Women’s Hospital examined a variety of tumors and found heavy expression of Sb9, which, in normal immune cells, acts as a shield against the cell’s own destructive enzymes (GrB).
The team then used CRISPR-Cas9 to engineer tumors that lack Sb9 – and found that those tumors grew at a slower rate in mice. They also observed Sb9 expression in cancer-associated fibroblasts and immunosuppressive cells surrounding the tumor, which promote cancer growth by weakening anti-cancer immune responses. When the engineered tumors were grown in Sb9-deficient mice, tumor growth was even slower.
As a result of these observations, the team developed a small-molecule Sb9 inhibitor, which proved effective in suppressing several murine models of solid tumors (1).
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References
- LJ Jiang, Cell, 183, 5, 1219 (2020). Available at: https://bit.ly/2JAB6rD.
