Cellular Immune Responses for Squamous Cell Carcinoma Antigen Recognized by T Cells 3 in Patients with Hepatocellular Carcinoma.
Squamous cell carcinoma antigen recognized by T cells 3 (SART3), a tumor-associated antigen expressed in many cancers, functions in tumor rejection. In this study, we investigated its usefulness as an immunotherapeutic target in hepatocellular carcinoma (HCC).The expression of SART3 in hepatoma cell...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5256867?pdf=render |
| _version_ | 1818912233519841280 |
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| author | Kiichiro Kaji Eishiro Mizukoshi Tatsuya Yamashita Kuniaki Arai Hajime Sunagozaka Kazumi Fushimi Hidetoshi Nakagawa Kazutoshi Yamada Takeshi Terashima Masaaki Kitahara Shuichi Kaneko |
| author_facet | Kiichiro Kaji Eishiro Mizukoshi Tatsuya Yamashita Kuniaki Arai Hajime Sunagozaka Kazumi Fushimi Hidetoshi Nakagawa Kazutoshi Yamada Takeshi Terashima Masaaki Kitahara Shuichi Kaneko |
| author_sort | Kiichiro Kaji |
| collection | DOAJ |
| description | Squamous cell carcinoma antigen recognized by T cells 3 (SART3), a tumor-associated antigen expressed in many cancers, functions in tumor rejection. In this study, we investigated its usefulness as an immunotherapeutic target in hepatocellular carcinoma (HCC).The expression of SART3 in hepatoma cell lines and HCC tissues was investigated by immunofluorescence and immunohistochemical analyses. Two peptides derived from SART3 (SART3109 and SART3315) were used for immunological analysis. T-cell responses were investigated by interferon-gamma (IFN-γ) enzyme-linked immunospot and cytotoxic T lymphocyte (CTL) assays using peripheral blood mononuclear cells (PBMCs) in 47 patients, and tumor-infiltrating lymphocytes in 8 of 47 patients with HCC. The safety of immunotherapy using a SART3-derived peptide was investigated by vaccinations of SART3109 in 12 patients with HCC (trial registration: UMIN000005677).The immunofluorescence and immunohistochemical analyses showed that SART3 was expressed in six HCC cell lines, and in HCC tissues including of alpha-fetoprotein-negative individuals. SART3-specific CTLs were generated by stimulating PBMCs with the peptides, and they showed cytotoxicity against HCC cells expressing the protein. Of the 47 HCC patients, 25.5% and 10.6% showed significant responses to SART3109 and SART3315, respectively. The infiltration of SART3109-specific IFN-γ-producing CTLs into the tumor site was confirmed. In the vaccination study, no severe adverse events were observed, and the peptide-specific CTLs were newly induced in four of five patients tested.SART3 is an immunotherapeutic candidate, and peptides from this antigen may be applied in HCC immunotherapy.UMIN000005677. |
| first_indexed | 2024-12-19T23:11:20Z |
| format | Article |
| id | doaj.art-177c0a26de6145ebaf3118a27ec4db4a |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-19T23:11:20Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-177c0a26de6145ebaf3118a27ec4db4a2022-12-21T20:02:12ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01121e017029110.1371/journal.pone.0170291Cellular Immune Responses for Squamous Cell Carcinoma Antigen Recognized by T Cells 3 in Patients with Hepatocellular Carcinoma.Kiichiro KajiEishiro MizukoshiTatsuya YamashitaKuniaki AraiHajime SunagozakaKazumi FushimiHidetoshi NakagawaKazutoshi YamadaTakeshi TerashimaMasaaki KitaharaShuichi KanekoSquamous cell carcinoma antigen recognized by T cells 3 (SART3), a tumor-associated antigen expressed in many cancers, functions in tumor rejection. In this study, we investigated its usefulness as an immunotherapeutic target in hepatocellular carcinoma (HCC).The expression of SART3 in hepatoma cell lines and HCC tissues was investigated by immunofluorescence and immunohistochemical analyses. Two peptides derived from SART3 (SART3109 and SART3315) were used for immunological analysis. T-cell responses were investigated by interferon-gamma (IFN-γ) enzyme-linked immunospot and cytotoxic T lymphocyte (CTL) assays using peripheral blood mononuclear cells (PBMCs) in 47 patients, and tumor-infiltrating lymphocytes in 8 of 47 patients with HCC. The safety of immunotherapy using a SART3-derived peptide was investigated by vaccinations of SART3109 in 12 patients with HCC (trial registration: UMIN000005677).The immunofluorescence and immunohistochemical analyses showed that SART3 was expressed in six HCC cell lines, and in HCC tissues including of alpha-fetoprotein-negative individuals. SART3-specific CTLs were generated by stimulating PBMCs with the peptides, and they showed cytotoxicity against HCC cells expressing the protein. Of the 47 HCC patients, 25.5% and 10.6% showed significant responses to SART3109 and SART3315, respectively. The infiltration of SART3109-specific IFN-γ-producing CTLs into the tumor site was confirmed. In the vaccination study, no severe adverse events were observed, and the peptide-specific CTLs were newly induced in four of five patients tested.SART3 is an immunotherapeutic candidate, and peptides from this antigen may be applied in HCC immunotherapy.UMIN000005677.http://europepmc.org/articles/PMC5256867?pdf=render |
| spellingShingle | Kiichiro Kaji Eishiro Mizukoshi Tatsuya Yamashita Kuniaki Arai Hajime Sunagozaka Kazumi Fushimi Hidetoshi Nakagawa Kazutoshi Yamada Takeshi Terashima Masaaki Kitahara Shuichi Kaneko Cellular Immune Responses for Squamous Cell Carcinoma Antigen Recognized by T Cells 3 in Patients with Hepatocellular Carcinoma. PLoS ONE |
| title | Cellular Immune Responses for Squamous Cell Carcinoma Antigen Recognized by T Cells 3 in Patients with Hepatocellular Carcinoma. |
| title_full | Cellular Immune Responses for Squamous Cell Carcinoma Antigen Recognized by T Cells 3 in Patients with Hepatocellular Carcinoma. |
| title_fullStr | Cellular Immune Responses for Squamous Cell Carcinoma Antigen Recognized by T Cells 3 in Patients with Hepatocellular Carcinoma. |
| title_full_unstemmed | Cellular Immune Responses for Squamous Cell Carcinoma Antigen Recognized by T Cells 3 in Patients with Hepatocellular Carcinoma. |
| title_short | Cellular Immune Responses for Squamous Cell Carcinoma Antigen Recognized by T Cells 3 in Patients with Hepatocellular Carcinoma. |
| title_sort | cellular immune responses for squamous cell carcinoma antigen recognized by t cells 3 in patients with hepatocellular carcinoma |
| url | http://europepmc.org/articles/PMC5256867?pdf=render |
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