Immune checkpoint therapy in liver cancer
Abstract Immune checkpoints include stimulatory and inhibitory checkpoint molecules. In recent years, inhibitory checkpoints, including cytotoxic T lymphocyte–associated antigen 4 (CTLA-4), programmed cell death protein-1 (PD-1), and programmed cell death ligand 1 (PD-L1), have been identified to su...
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| Format: | Article |
| Language: | English |
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BMC
2018-05-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
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| Online Access: | http://link.springer.com/article/10.1186/s13046-018-0777-4 |
| _version_ | 1818310908013707264 |
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| author | Feng Xu Tianqiang Jin Yuwen Zhu Chaoliu Dai |
| author_facet | Feng Xu Tianqiang Jin Yuwen Zhu Chaoliu Dai |
| author_sort | Feng Xu |
| collection | DOAJ |
| description | Abstract Immune checkpoints include stimulatory and inhibitory checkpoint molecules. In recent years, inhibitory checkpoints, including cytotoxic T lymphocyte–associated antigen 4 (CTLA-4), programmed cell death protein-1 (PD-1), and programmed cell death ligand 1 (PD-L1), have been identified to suppress anti-tumor immune responses in solid tumors. Novel drugs targeting immune checkpoints have succeeded in cancer treatment. Specific PD-1 blockades were approved for treatment of melanoma in 2014 and for treatment of non-small-cell lung cancer in 2015 in the United States, European Union, and Japan. Preclinical and clinical studies show immune checkpoint therapy provides survival benefit for greater numbers of patients with liver cancer, including hepatocellular carcinoma and cholangiocarcinoma, two main primary liver cancers. The combination of anti-PD-1/PD-L1 with anti-CTLA-4 antibodies is being evaluated in phase 1, 2 or 3 trials, and the results suggest that an anti-PD-1 antibody combined with locoregional therapy or other molecular targeted agents is an effective treatment strategy for HCC. In addition, studies on activating co-stimulatory receptors to enhance anti-tumor immune responses have increased our understanding regarding this immunotherapy in liver cancer. Epigenetic modulations of checkpoints for improving the tumor microenvironment also expand our knowledge of potential therapeutic targets in improving the tumor microenvironment and restoring immune recognition and immunogenicity. In this review, we summarize current knowledge and recent developments in immune checkpoint-based therapies for the treatment of hepatocellular carcinoma and cholangiocarcinoma and attempt to clarify the mechanisms underlying its effects. |
| first_indexed | 2024-12-13T07:53:32Z |
| format | Article |
| id | doaj.art-de5b3e9675054926b46bdca97de031fd |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-12-13T07:53:32Z |
| publishDate | 2018-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-de5b3e9675054926b46bdca97de031fd2022-12-21T23:54:37ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662018-05-0137111210.1186/s13046-018-0777-4Immune checkpoint therapy in liver cancerFeng Xu0Tianqiang Jin1Yuwen Zhu2Chaoliu Dai3Department of Hepatobiliary and Splenic Surgery, Shengjing Hospital affiliated to China Medical UniversityDepartment of Hepatobiliary and Splenic Surgery, Shengjing Hospital affiliated to China Medical UniversityDepartment of Surgery, University of Colorado Anschutz Medical CampusDepartment of Hepatobiliary and Splenic Surgery, Shengjing Hospital affiliated to China Medical UniversityAbstract Immune checkpoints include stimulatory and inhibitory checkpoint molecules. In recent years, inhibitory checkpoints, including cytotoxic T lymphocyte–associated antigen 4 (CTLA-4), programmed cell death protein-1 (PD-1), and programmed cell death ligand 1 (PD-L1), have been identified to suppress anti-tumor immune responses in solid tumors. Novel drugs targeting immune checkpoints have succeeded in cancer treatment. Specific PD-1 blockades were approved for treatment of melanoma in 2014 and for treatment of non-small-cell lung cancer in 2015 in the United States, European Union, and Japan. Preclinical and clinical studies show immune checkpoint therapy provides survival benefit for greater numbers of patients with liver cancer, including hepatocellular carcinoma and cholangiocarcinoma, two main primary liver cancers. The combination of anti-PD-1/PD-L1 with anti-CTLA-4 antibodies is being evaluated in phase 1, 2 or 3 trials, and the results suggest that an anti-PD-1 antibody combined with locoregional therapy or other molecular targeted agents is an effective treatment strategy for HCC. In addition, studies on activating co-stimulatory receptors to enhance anti-tumor immune responses have increased our understanding regarding this immunotherapy in liver cancer. Epigenetic modulations of checkpoints for improving the tumor microenvironment also expand our knowledge of potential therapeutic targets in improving the tumor microenvironment and restoring immune recognition and immunogenicity. In this review, we summarize current knowledge and recent developments in immune checkpoint-based therapies for the treatment of hepatocellular carcinoma and cholangiocarcinoma and attempt to clarify the mechanisms underlying its effects.http://link.springer.com/article/10.1186/s13046-018-0777-4Immune checkpointHepatocellular carcinomaCholangiocarcinomaImmunotherapyEpigenetics |
| spellingShingle | Feng Xu Tianqiang Jin Yuwen Zhu Chaoliu Dai Immune checkpoint therapy in liver cancer Journal of Experimental & Clinical Cancer Research Immune checkpoint Hepatocellular carcinoma Cholangiocarcinoma Immunotherapy Epigenetics |
| title | Immune checkpoint therapy in liver cancer |
| title_full | Immune checkpoint therapy in liver cancer |
| title_fullStr | Immune checkpoint therapy in liver cancer |
| title_full_unstemmed | Immune checkpoint therapy in liver cancer |
| title_short | Immune checkpoint therapy in liver cancer |
| title_sort | immune checkpoint therapy in liver cancer |
| topic | Immune checkpoint Hepatocellular carcinoma Cholangiocarcinoma Immunotherapy Epigenetics |
| url | http://link.springer.com/article/10.1186/s13046-018-0777-4 |
| work_keys_str_mv | AT fengxu immunecheckpointtherapyinlivercancer AT tianqiangjin immunecheckpointtherapyinlivercancer AT yuwenzhu immunecheckpointtherapyinlivercancer AT chaoliudai immunecheckpointtherapyinlivercancer |