- [IMMUNOLOGY AND IMMUNOTHERAPY]
- [COMBINATION STRATEGIES FOR TRANSLATIONAL IMMUNOTHERAPY]
- [CYTOKINE-BASED THERAPEUTICS]
Immune Desertic Landscapes in Hepatocellular Carcinoma Shaped by β-Catenin Activation
Berraondo P (1,2,3), Ochoa MC (1,2,3,4), Olivera I (1,2), Melero I (5,2,3,4).
About one third of cases of hepatocellular carcinoma (HCC) show gain-of-function mutations of CTNNB1 (β-catenin) that correlate with sparse intratumoral T-cell content, as observed previously in an ample spectrum of malignancies, and there is mounting preliminary evidence that such HCC cases are refractory to treatment with PD-1 checkpoint inhibitors.
Elegant hepatocarcinogenesis experiments by in vivo gene transfer to mouse hepatocytes show that coexpression of active forms of β-catenin result in poor T-cell infiltrates, faster progression in immunocompetent hosts, and unresponsiveness to immunotherapy with checkpoint inhibitors.See related article by Ruiz de Galarreta et al., p. 1124.
© 2019 American Association for Cancer Research.
CITATION Cancer Discov. 2019 Aug;9(8):1003-1005. doi: 10.1158/2159-8290.CD-19-0696