Kevin Bévant, C. Coulouarn
EBioMedicine, 2020
Liver cancer, including hepatocellular carcinoma (HCC), is the 4th leading cause of cancer-related death worldwide, notably as a result of tumor heterogeneity which hampers the development of efficient treatments. Integrative genomics helped with characterizing heterogeneity in cancer, leading to molecular stratification of tumors and adapted therapeutic strategies for specific tumor subtypes. In this article of EBioMedicine, Fujita and colleagues report the results of an elegant meta-analysis of RNA and whole genome sequencing data from 234 liver primary tumors [1]. Based on immune signatures and genomic alterations, four tumor subtypes are highlighted. Three subtypes exhibit mutually exclusive immunosuppressive features associated with infiltration of regulatory T cells or tumor-associated macrophages (TAM) and CTNNB1 mutations. One subtype associated with a better prognosis shows cytolytic activity. The study brings important information on the immunosuppressive properties of HCC microenvironment. Notably, the non-inflamed TAM subtype is enriched in ARID2 mutations resulting in impairment of chemokine production and a weaker inflammatory and interferong response. By taking into account immunosuppressive mechanisms, the study improves the current binary immune classification into “inflamed” or “non-inflamed” tumors. From a clinical perspective, understanding HCC immunosuppressive properties is critical to improve the efficacy of immune-based therapeutic strategies. Over the last decade, immune checkpoint inhibitors and CAR-T cells emerged as innovative therapeutic options. Both have shown promising results in several cancers but not in liver cancer, particularly as a result of frequent intrinsic tumor immunosuppression [2,3]. Notably, CAR-T cell therapy is hampered in HCC by the limited migration of T cell into the tumor, the immunosuppressive tumor microenvironment and the lack of well-defined tumor antigens [4].
Cited by 2 publications.
Field of study: Medicine