- [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).
(1) Program of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, Spain.
(2) Navarra Institute for Health Research (IDISNA), Pamplona, Spain.
(3) Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Spain.
(4) Department of Immunology and Immunotherapy, Clinica Universidad de Navarra, Pamplona, Spain.
(5) Program of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, Spain.
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