Immune checkpoint inhibitors in HCC: Cellular, molecular and systemic data. (November 2022)

• Record Type: Journal Article
• Authors: Harkus, Uasim; Wankell, Miriam; Palamuthusingam, Pranavan; McFarlane, Craig; Hebbard, Lionel
• Is Part Of: Seminars in cancer biology. Volume 86(2023)Part 3
• Page Start: 799
• Page End: 815
• Publication Date: 2022-11
• Subjects: 4−1BB TNF Receptor Superfamily Member 9 -- AFP Alpha-fetoprotein -- Akt Protein kinase B -- AREG Amphiregulin -- ARG1 Arginase 1 -- ATAR All trans-retinoic acid -- β2M β2-microglobulin -- Bregs regulatory B cells -- BTLA B- and T-lymphocyte attenuator -- CCL Chemokine (CC motif) ligand -- CCR C-C chemokine receptor -- CD Cluster of differentiation -- CI Confidence interval -- CSCs Cancer stem cells -- CSF-1 Colony stimulating factor 1 -- CSF1R Colony stimulating factor 1 receptor -- CTGF Connective tissue growth factor -- CTLA-4 Cytotoxic T-lymphocyte–associated antigen 4 -- CXCL C-X-C Motif Chemokine Ligand -- CXCR CXC chemokine receptor -- DCR Disease control rate -- DNMT1 DNA Methyltransferase 1 -- EGFR Epidermal growth factor receptor -- Eomes Eomesodermin -- EZH2 Enhancer of Zeste Homolog 2 -- FasL Fas ligand -- FENDRR FOXF1 Adjacent Non-Coding Developmental Regulatory RNA -- FGF Fibroblast growth factors -- FGL1 Fibrinogen-like protein 1 -- G-CSF Granulocyte colony-stimulating factor -- GITR Glucocorticoid-induced tumour necrosis factor receptor -- GM-CSF Granulocyte-macrophage colony-stimulating factor -- GPC‐3 Glypican 3 -- HR Hazard ratio -- HDACi histone deacetylase inhibitor -- HGF Hepatocyte growth factor -- HLA Human leukocyte antigen -- ICI Immune checkpoint inhibitors -- IDO Indoleamine 2, 3 dioxygenase -- IFN Interferon -- IL Interleukin -- ILCs innate lymphoid cells -- iNOS inducible Nitric oxide synthase -- JAK/STAT Janus Kinase and Signal Transducer and Activator of Transcription -- LAG-3 Lymphocyte Activation Gene-3 -- LILRB1 Leukocyte immunoglobulin-like receptor subfamily B member 1 -- lncRNA Long noncoding RNA -- Lnc-EGFR Long noncoding RNA Epidermal growth factor receptor -- lncRNA DANCR Long noncoding RNA Differentiation antagonizing nonprotein coding RNA -- lncRNA PRR34-AS1 Long noncoding RNA PRR34 antisense RNA 1 -- Lnc-Tim3 long noncoding RNA T cell immunoglobulin and mucin domain-containing protein 3 -- mAb monoclonal antibody -- MAGE‐A1 Melanoma-associated antigen A1 -- MAPK Mitogen-activated protein kinase -- MDSCs Myeloid derived suppressor cells -- MHC Major histocompatibility complex -- MMP Metalloproteinase -- MTOR Mammalian target of rapamycin -- NEAT1 Nuclear paraspeckle assembly transcript 1 -- NF-κB Nuclear Factor kappa-light-chain-enhancer of activated B cells -- NKG2A Natural kill er group 2 member D -- NKG2D Natural killer group 2 member D -- NKG2DL Natural killer group 2 member D ligand -- NOS Nitric oxide synthases -- NSCLC Non-small cell lung cancer -- NY‐ESO‐1 New York oesophageal squamous cell carcinoma 1 -- OPN Osteopontin -- OS Overall survival -- ORR Objective response rate -- OX40 Tumor necrosis factor receptor superfamily, member 4 -- PD1/ PD-1 Programmed cell death protein 1 -- PDE5 Phosphodiesterase type 5 -- PDGF Platelet derived growth factor -- PD-L1 Programmed cell death ligand 1/ Programmed death-ligand 1 -- PFS Progression free survival -- PGE-2 Prostaglandin E 2 -- PI3K Phosphoinositide 3 kinase -- PRR Partial response rate -- PTPN2 Protein tyrosine phosphatase non-receptor type 2 -- PVR Poliovirus receptor -- ROS Reactive oxygen species -- STAT-3 Signal transducer and activator of transcription -- TAA Tumour associated antigens -- TCR T cell receptor -- TGF-β Transforming growth factor beta -- Th1 T helper 1 -- Th2 T helper 2 -- TIGIT T cell immunoreceptor with Ig and ITIM domains -- TIM-3 T cell immunoglobulin and mucin domain-containing protein 3 -- TKI Tyrosine kinase inhibitors -- TLR Toll like receptor -- TMB tumour mutational burden -- TNFR Tumor necrosis factor receptor -- TNF-α Tumor necrosis factor-alpha -- TRAIL Tumor necrosis factor-related apoptosis-inducing ligand -- TREM Triggering receptors expressed by myeloid cells -- VEGF Vascular endothelial growth factor -- VEGFR2 Vascular endothelial growth factor receptor 2 -- VISTA V-domain immunoglobulin suppressor of T-cell activation -- VTCN1 V-set domain-containing T-cell activation inhibitor 1 -- Wnt/β-catenin Wingless/β-catenin; Hepatocellular carcinoma -- Immunotherapy -- Immune checkpoints; Cancer -- Periodicals; Neoplasms -- Periodicals; Review Literature; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.semcancer.2022.01.005
• Languages: English
• ISSNs: 1044-579X

Abstract

Highlights: HCC is a poorly treated cancer and its incidence is increasing rapidly worldwide. The combination of checkpoint inhibitors and anti-angiogenic therapy has improved survival in patients with unresectable HCC. Some patients respond well to checkpoint inhibitors, but many attain no benefit or in some cases progress. Modulating the immune response in HCC patients may be beneficial for improving response to checkpoint inhibitor therapy. Numerous clinical trials are underway to develop more personalised HCC therapy. Abstract: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer related deaths in the world, and for patients with advanced disease there are few therapeutic options available. The complex immunological microenvironment of HCC and the success of immunotherapy in several types of tumours, has raised the prospect of potential benefit for immune based therapies, such as immune checkpoint inhibitors (ICIs), in HCC. This has led to significant breakthrough research, numerous clinical trials and the rapid approval of multiple systemic drugs for HCC by regulatory bodies worldwide. Although some patients responded well to ICIs, many have failed to achieve significant benefit, while others showed unexpected and paradoxical deterioration. The aim of this review is to discuss the pathophysiology of HCC, the tumour microenvironment, key clinical trials evaluating ICIs in HCC, various resistance mechanisms to ICIs, and possible ways to overcome these impediments to improve patient outcomes.