Inhibition of DUSP18 for antitumor immunity in colorectal cancer

Inhibiting DUSP18, a phosphatase that stabilizes the transcription factor USF1 to promote expression of the cholesterol biosynthesis pathway, could help treat colorectal cancer by decreasing tumor cell production of the immunosuppressive cholesterol intermediate lanosterol, thus increasing CD8⁺ T cell activation and antitumor immunity.

In a syngenic mouse model of colorectal cancer, a CRISPR/Cas9 loss-of-function screen for kinases and phosphatases identified DUSP18 as a regulator of antitumor immunity and immune evasion...