Strategies to Improve the Antitumor Effect of Immunotherapy for Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC), one of the most fatal malignancies in the world, is usually diagnosed in advanced stages due to late symptom manifestation with very limited therapeutic options, which leads to ineffective intervention and dismal prognosis. For a decade, tyrosine kinase inhibitors (TK...

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Autores principales: Rui Xing, Jinping Gao, Qi Cui, Qian Wang
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Publicado: Frontiers Media S.A. 2021
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spelling oai:doaj.org-article:4df16459bfcb422d82a06d08fb6c79aa2021-12-01T04:47:01ZStrategies to Improve the Antitumor Effect of Immunotherapy for Hepatocellular Carcinoma1664-322410.3389/fimmu.2021.783236https://doaj.org/article/4df16459bfcb422d82a06d08fb6c79aa2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.783236/fullhttps://doaj.org/toc/1664-3224Hepatocellular carcinoma (HCC), one of the most fatal malignancies in the world, is usually diagnosed in advanced stages due to late symptom manifestation with very limited therapeutic options, which leads to ineffective intervention and dismal prognosis. For a decade, tyrosine kinase inhibitors (TKIs) have offered an overall survival (OS) benefit when used in a first-line (sorafenib and lenvatinib) and second-line setting (regorafenib and cabozantinib) in advanced HCC, while long-term response remains unsatisfactory due to the onset of primary or acquired resistance. Recently, immunotherapy has emerged as a promising therapy in the treatment of several solid tumors, such as melanoma and non-small cell lung cancer. Moreover, as the occurrence of HCC is associated with immune tolerance and immunosurveillance escape, there is a potent rationale for employing immunotherapy in HCC. However, immunotherapy monotherapy, mainly including immune checkpoint inhibitors (ICIs) that target checkpoints programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), and the cytotoxic T lymphocyte antigen-4 (CTLA-4), has a relatively low response rate. Thus, the multi-ICIs or the combination of immunotherapy with other therapies, like antiangiogenic drugs and locoregional therapies, has become a novel strategy to treat HCC. Combining different ICIs may have a synergistical effect attributed to the complementary effects of the two immune checkpoint pathways (CTLA-4 and PD-1/PD-L1 pathways). The incorporation of antiangiogenic drugs in ICIs can enhance antitumor immune responses via synergistically regulating the vasculature and the immune microenvironment of tumor. In addition, locoregional treatments can improve antitumor immunity by releasing the neoplasm antigens from killed tumor cells; in turn, this antitumor immune response can be intensified by immunotherapy. Therefore, the combination of locoregional treatments and immunotherapy may achieve greater efficacy through further synergistic effects for advanced HCC. This review aims to summarize the currently reported results and ongoing trials of the ICIs-based combination therapies for HCC to explore the rational combination strategies and further improve the survival of patients with HCC.Rui XingJinping GaoQi CuiQian WangFrontiers Media S.A.articlehepatocellular carcinomaimmune checkpoint inhibitorscombination therapyantiangiogenic drugslocoregional therapiesImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution DOAJ
collection DOAJ
language EN
topic hepatocellular carcinoma
immune checkpoint inhibitors
combination therapy
antiangiogenic drugs
locoregional therapies
Immunologic diseases. Allergy
RC581-607
spellingShingle hepatocellular carcinoma
immune checkpoint inhibitors
combination therapy
antiangiogenic drugs
locoregional therapies
Immunologic diseases. Allergy
RC581-607
Rui Xing
Jinping Gao
Qi Cui
Qian Wang
Strategies to Improve the Antitumor Effect of Immunotherapy for Hepatocellular Carcinoma
description Hepatocellular carcinoma (HCC), one of the most fatal malignancies in the world, is usually diagnosed in advanced stages due to late symptom manifestation with very limited therapeutic options, which leads to ineffective intervention and dismal prognosis. For a decade, tyrosine kinase inhibitors (TKIs) have offered an overall survival (OS) benefit when used in a first-line (sorafenib and lenvatinib) and second-line setting (regorafenib and cabozantinib) in advanced HCC, while long-term response remains unsatisfactory due to the onset of primary or acquired resistance. Recently, immunotherapy has emerged as a promising therapy in the treatment of several solid tumors, such as melanoma and non-small cell lung cancer. Moreover, as the occurrence of HCC is associated with immune tolerance and immunosurveillance escape, there is a potent rationale for employing immunotherapy in HCC. However, immunotherapy monotherapy, mainly including immune checkpoint inhibitors (ICIs) that target checkpoints programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), and the cytotoxic T lymphocyte antigen-4 (CTLA-4), has a relatively low response rate. Thus, the multi-ICIs or the combination of immunotherapy with other therapies, like antiangiogenic drugs and locoregional therapies, has become a novel strategy to treat HCC. Combining different ICIs may have a synergistical effect attributed to the complementary effects of the two immune checkpoint pathways (CTLA-4 and PD-1/PD-L1 pathways). The incorporation of antiangiogenic drugs in ICIs can enhance antitumor immune responses via synergistically regulating the vasculature and the immune microenvironment of tumor. In addition, locoregional treatments can improve antitumor immunity by releasing the neoplasm antigens from killed tumor cells; in turn, this antitumor immune response can be intensified by immunotherapy. Therefore, the combination of locoregional treatments and immunotherapy may achieve greater efficacy through further synergistic effects for advanced HCC. This review aims to summarize the currently reported results and ongoing trials of the ICIs-based combination therapies for HCC to explore the rational combination strategies and further improve the survival of patients with HCC.
format article
author Rui Xing
Jinping Gao
Qi Cui
Qian Wang
author_facet Rui Xing
Jinping Gao
Qi Cui
Qian Wang
author_sort Rui Xing
title Strategies to Improve the Antitumor Effect of Immunotherapy for Hepatocellular Carcinoma
title_short Strategies to Improve the Antitumor Effect of Immunotherapy for Hepatocellular Carcinoma
title_full Strategies to Improve the Antitumor Effect of Immunotherapy for Hepatocellular Carcinoma
title_fullStr Strategies to Improve the Antitumor Effect of Immunotherapy for Hepatocellular Carcinoma
title_full_unstemmed Strategies to Improve the Antitumor Effect of Immunotherapy for Hepatocellular Carcinoma
title_sort strategies to improve the antitumor effect of immunotherapy for hepatocellular carcinoma
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/4df16459bfcb422d82a06d08fb6c79aa
work_keys_str_mv AT ruixing strategiestoimprovetheantitumoreffectofimmunotherapyforhepatocellularcarcinoma
AT jinpinggao strategiestoimprovetheantitumoreffectofimmunotherapyforhepatocellularcarcinoma
AT qicui strategiestoimprovetheantitumoreffectofimmunotherapyforhepatocellularcarcinoma
AT qianwang strategiestoimprovetheantitumoreffectofimmunotherapyforhepatocellularcarcinoma
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