Hepatocellular Carcinoma Immune Landscape and the Potential of Immunotherapies
Hepatocellular carcinoma (HCC) is the most common liver tumor and among the deadliest cancers worldwide. Advanced HCC overall survival is meager and has not improved over the last decade despite approval of several tyrosine kinase inhibitors (TKi) for first and second-line treatments. The recent app...
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doaj-78944b22f11b4e14b0db4d7295a4281a2021-03-18T06:45:13ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-03-011210.3389/fimmu.2021.655697655697Hepatocellular Carcinoma Immune Landscape and the Potential of ImmunotherapiesJulie Giraud0Domitille Chalopin1Jean-Frédéric Blanc2Jean-Frédéric Blanc3Maya Saleh4Maya Saleh5University of Bordeaux, CNRS, ImmunoConcEpT, UMR 5164, Bordeaux, FranceUniversity of Bordeaux, CNRS, ImmunoConcEpT, UMR 5164, Bordeaux, FranceUniversity of Bordeaux, INSERM UMR 1053, Bordeaux, FranceDepartment of Oncology, CHU Bordeaux, Haut Leveque Hospital, Pessac, FranceUniversity of Bordeaux, CNRS, ImmunoConcEpT, UMR 5164, Bordeaux, FranceDepartment of Medicine, McGill University, Montreal, QC, CanadaHepatocellular carcinoma (HCC) is the most common liver tumor and among the deadliest cancers worldwide. Advanced HCC overall survival is meager and has not improved over the last decade despite approval of several tyrosine kinase inhibitors (TKi) for first and second-line treatments. The recent approval of immune checkpoint inhibitors (ICI) has revolutionized HCC palliative care. Unfortunately, the majority of HCC patients fail to respond to these therapies. Here, we elaborate on the immune landscapes of the normal and cirrhotic livers and of the unique HCC tumor microenvironment. We describe the molecular and immunological classifications of HCC, discuss the role of specific immune cell subsets in this cancer, with a focus on myeloid cells and pathways in anti-tumor immunity, tumor promotion and immune evasion. We also describe the challenges and opportunities of immunotherapies in HCC and discuss new avenues based on harnessing the anti-tumor activity of myeloid, NK and γδ T cells, vaccines, chimeric antigen receptors (CAR)-T or -NK cells, oncolytic viruses, and combination therapies.https://www.frontiersin.org/articles/10.3389/fimmu.2021.655697/fullimmunotherapyimmune checkpoint inhibitorstumor microenvironmenttumor-associated macrophagesimmunosuppressioninflammation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Julie Giraud Domitille Chalopin Jean-Frédéric Blanc Jean-Frédéric Blanc Maya Saleh Maya Saleh |
spellingShingle |
Julie Giraud Domitille Chalopin Jean-Frédéric Blanc Jean-Frédéric Blanc Maya Saleh Maya Saleh Hepatocellular Carcinoma Immune Landscape and the Potential of Immunotherapies Frontiers in Immunology immunotherapy immune checkpoint inhibitors tumor microenvironment tumor-associated macrophages immunosuppression inflammation |
author_facet |
Julie Giraud Domitille Chalopin Jean-Frédéric Blanc Jean-Frédéric Blanc Maya Saleh Maya Saleh |
author_sort |
Julie Giraud |
title |
Hepatocellular Carcinoma Immune Landscape and the Potential of Immunotherapies |
title_short |
Hepatocellular Carcinoma Immune Landscape and the Potential of Immunotherapies |
title_full |
Hepatocellular Carcinoma Immune Landscape and the Potential of Immunotherapies |
title_fullStr |
Hepatocellular Carcinoma Immune Landscape and the Potential of Immunotherapies |
title_full_unstemmed |
Hepatocellular Carcinoma Immune Landscape and the Potential of Immunotherapies |
title_sort |
hepatocellular carcinoma immune landscape and the potential of immunotherapies |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2021-03-01 |
description |
Hepatocellular carcinoma (HCC) is the most common liver tumor and among the deadliest cancers worldwide. Advanced HCC overall survival is meager and has not improved over the last decade despite approval of several tyrosine kinase inhibitors (TKi) for first and second-line treatments. The recent approval of immune checkpoint inhibitors (ICI) has revolutionized HCC palliative care. Unfortunately, the majority of HCC patients fail to respond to these therapies. Here, we elaborate on the immune landscapes of the normal and cirrhotic livers and of the unique HCC tumor microenvironment. We describe the molecular and immunological classifications of HCC, discuss the role of specific immune cell subsets in this cancer, with a focus on myeloid cells and pathways in anti-tumor immunity, tumor promotion and immune evasion. We also describe the challenges and opportunities of immunotherapies in HCC and discuss new avenues based on harnessing the anti-tumor activity of myeloid, NK and γδ T cells, vaccines, chimeric antigen receptors (CAR)-T or -NK cells, oncolytic viruses, and combination therapies. |
topic |
immunotherapy immune checkpoint inhibitors tumor microenvironment tumor-associated macrophages immunosuppression inflammation |
url |
https://www.frontiersin.org/articles/10.3389/fimmu.2021.655697/full |
work_keys_str_mv |
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