• HEPATOCELLULAR CARCINOMA
• IMMUNOLOGY IN HEPATOLOGY
• IMMUNOTHERAPY

Data from the United States, Surveillance, Epidemiology, and End Results Program reveal that hepatocellular carcinoma (HCC) 5-year relative survival is 20.3% (https://seer.cancer.gov/statfacts/html/livibd.html). ‘Approximately, 1.0% of men and women will be diagnosed with liver and intrahepatic bile duct cancer at some point during their lifetime, based on 2016–2018 data’. And yet, in the 45% confined to the liver, the 5-year relative survival is 35.3%. Notably, 50%–60% of patients with HCC will receive systemic therapies,1 including immune check-point inhibitors (ICIs). The overall response rate to ICIs ranges from 7% to 36%, thus understanding who may benefit (cui bono? Marcus Tullius Cicero, https://www.britannica.com/biography/Cicero) from these immune-based therapies can be a game-changer in HCC therapy. In a work published in Gut, Montironi et al performed a molecular phenotyping study to dissect the immunogenomic patterns to predict ICIs response.2 The first thorough immune classification of HCC was reported in 2017 by this same group, implementing a transcriptomic deconvolution approach.3 This previous study identified an ‘immune class’ accounting for 25% of HCCs, which included an ‘immune active’ subclass rich in interferon (IFN) signalling and adaptive immune response with favourable prognosis and an ‘immune exhausted’ subclass abundant in immunosuppressive components. In the current study, using a complex discovery and external validation design, the authors studied 900 patients with HCC via RNA and whole-exome sequencing, T-cell receptor-sequencing, multiplex immunofluorescence and immunohistochemistry. The authors found 35% of HCCs pertaining to the so-called ‘inflamed class’, which expanded the previous ‘immune class’ and could be subdivided into the (a) active and (b) exhausted subclasses and (c) a new immune-like subclass. In contrast, 65% of HCCs were in the non-inflamed class, …