The summaries are free for public
use. The Chronic Liver Disease
Foundation will continue to add and
archive summaries of articles deemed
relevant to CLDF by the Board of
Trustees and its Advisors.
1Mount Sinai Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. josep.llovet@mountsinai.org.
2Translational Research in Hepatic Oncology, Liver Unit, IDIBAPS, Hospital Clinic, University of Barcelona, Barcelona, Spain. josep.llovet@mountsinai.org.
3Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain. josep.llovet@mountsinai.org.
4Translational Research in Hepatic Oncology, Liver Unit, IDIBAPS, Hospital Clinic, University of Barcelona, Barcelona, Spain.
5Division of Chronic Inflammation and Cancer, German Cancer Research Centre Heidelberg (DKFZ), Heidelberg, Germany.
6Division of Infection & Immunity, Institute of Immunity & Transplantation, University College London, London, UK.
7Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
8HPB Surgery, Hepatology and Liver Transplantation, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan, Italy.
9Department of Surgery & Cancer, Imperial College London, Hammersmith Hospital, London, UK.
10Department of Translational Medicine, Division of Oncology, University of Piemonte Orientale, Novara, Italy.
11The Lautenberg Center for Immunology and Cancer Research, IMRIC, The Hebrew University of Jerusalem, Jerusalem, Israel.
12Massachusetts General Hospital Cancer Center, Boston, MA, USA.
13Jiahui International Cancer Center, Jiahui Health, Shanghai, China.
14Ronald Reagan University of California, Los Angeles (UCLA) Medical Center, Los Angeles, CA, USA.
Abstract
Liver cancer, more specifically hepatocellular carcinoma (HCC), is the second leading cause of cancer-related death and its incidence is increasing globally. Around 50% of patients with HCC receive systemic therapies, traditionally sorafenib or lenvatinib in the first line and regorafenib, cabozantinib or ramucirumab in the second line. In the past 5 years, immune-checkpoint inhibitors have revolutionized the management of HCC. The combination of atezolizumab and bevacizumab has been shown to improve overall survival relative to sorafenib, resulting in FDA approval of this regimen. More recently, durvalumab plus tremelimumab yielded superior overall survival versus sorafenib and atezolizumab plus cabozantinib yielded superior progression-free survival. In addition, pembrolizumab monotherapy and the combination of nivolumab plus ipilimumab have received FDA Accelerated Approval in the second-line setting based on early efficacy data. Despite these major advances, the molecular underpinnings governing immune responses and evasion remain unclear. The immune microenvironment has crucial roles in the development and progression of HCC and distinct aetiology-dependent immune features have been defined. Inflamed and non-inflamed classes of HCC and genomic signatures have been associated with response to immune-checkpoint inhibitors, yet no validated biomarker is available to guide clinical decision-making. This Review provides information on the immune microenvironments underlying the response or resistance of HCC to immunotherapies. In addition, current evidence from phase III trials on the efficacy, immune-related adverse events and aetiology-dependent mechanisms of response are described. Finally, we discuss emerging trials assessing immunotherapies across all stages of HCC that might change the management of this disease in the near future.