Two Faces of NOTCH1 in Liver Cancer and Immunotherapy

High NOTCH1 expression inversely correlates with hepatocellular carcinoma tumorigenicity and contributes to better immune checkpoint inhibitor responses in male patients, whereas high NOTCH1 in females coincides with heightened hepatocellular carcinoma incidence and poor immunotherapy responses. Activated NOTCH1 generates enhanced antitumor CD8+ T-cell responses in a sex chromosome-dependent manner and facilitates responsiveness to immunotherapy treatment in males, whereas it drives immune escape in females. See related article by Lindblad et al., p. 495.