Total HLA Class I Antigen Loss with the Downregulation of Antigen-Processing Machinery Components in Two Newly Established Sarcomatoid Hepatocellular Carcinoma Cell Lines
Limited information is currently available concerning HLA class I antigen abnormalities in sarcomatoid hepatocellular carcinoma (sHCC). Here, we have analyzed the growth characteristics and HLA class I antigen status of four sHCC cell lines (sHCC29, sHCC63, sHCC74, and SAR-HCV); the first three were...
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2018-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2018/8363265 |
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| author | Wei-Yi Lei Shih-Chieh Hsiung Shao-Hsuan Wen Chin-Hsuan Hsieh Chien-Lin Chen Christopher Glenn Wallace Chien-Chung Chang Shuen-Kuei Liao |
| author_facet | Wei-Yi Lei Shih-Chieh Hsiung Shao-Hsuan Wen Chin-Hsuan Hsieh Chien-Lin Chen Christopher Glenn Wallace Chien-Chung Chang Shuen-Kuei Liao |
| author_sort | Wei-Yi Lei |
| collection | DOAJ |
| description | Limited information is currently available concerning HLA class I antigen abnormalities in sarcomatoid hepatocellular carcinoma (sHCC). Here, we have analyzed the growth characteristics and HLA class I antigen status of four sHCC cell lines (sHCC29, sHCC63, sHCC74, and SAR-HCV); the first three were newly established in this study. Among the four, sHCC29 showed the highest growth rate in vitro and tumorigenicity in NOD-SCID mice. Unlike sHCC74 and SAR-HCV, both sHCC29 and sHCC63 had no detectable surface HLA class I antigen expression, alongside undetected intracellular β2-microglobulin (β2m) and marked HLA class I heavy chain and selective antigen-processing machinery (APM) component downregulation. The loss of β2m in sHCC29 and sHCC63 was caused by a >49 kb deletion across the B2M locus, while their downregulation of APM components was transcriptional, reversible by IFN-γ only in several components. β2m was also undetected in the primary HCC lesions of the patients involved, indicating its in vivo relevance. We report for the first time HLA class I antigen loss with underlying B2M gene deficiency and APM defects in 50% (2 of 4) of the sHCC cell lines tested. These findings may have implications for a proper design of T cell immunotherapy for the treatment of sHCC patients. |
| format | Article |
| id | doaj-art-efda286b17704a038e89480a5eda7ccd |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-efda286b17704a038e89480a5eda7ccd2025-02-03T06:13:26ZengWileyJournal of Immunology Research2314-88612314-71562018-01-01201810.1155/2018/83632658363265Total HLA Class I Antigen Loss with the Downregulation of Antigen-Processing Machinery Components in Two Newly Established Sarcomatoid Hepatocellular Carcinoma Cell LinesWei-Yi Lei0Shih-Chieh Hsiung1Shao-Hsuan Wen2Chin-Hsuan Hsieh3Chien-Lin Chen4Christopher Glenn Wallace5Chien-Chung Chang6Shuen-Kuei Liao7Institute of Medical Sciences, Tzu Chi University, Hualien, TaiwanDivision of Urology, Department of Surgery, Chang Gung Memorial Hospital, Taoyuan, TaiwanInstitute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu, TaiwanDivision of Urology, Department of Surgery, Chang Gung Memorial Hospital, Taoyuan, TaiwanInstitute of Medical Sciences, Tzu Chi University, Hualien, TaiwanDepartment of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Taoyuan, TaiwanInstitute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu, TaiwanThe Ph.D. Program for Cancer Biology and Drug Discovery, Taipei Medical University, Taipei City, TaiwanLimited information is currently available concerning HLA class I antigen abnormalities in sarcomatoid hepatocellular carcinoma (sHCC). Here, we have analyzed the growth characteristics and HLA class I antigen status of four sHCC cell lines (sHCC29, sHCC63, sHCC74, and SAR-HCV); the first three were newly established in this study. Among the four, sHCC29 showed the highest growth rate in vitro and tumorigenicity in NOD-SCID mice. Unlike sHCC74 and SAR-HCV, both sHCC29 and sHCC63 had no detectable surface HLA class I antigen expression, alongside undetected intracellular β2-microglobulin (β2m) and marked HLA class I heavy chain and selective antigen-processing machinery (APM) component downregulation. The loss of β2m in sHCC29 and sHCC63 was caused by a >49 kb deletion across the B2M locus, while their downregulation of APM components was transcriptional, reversible by IFN-γ only in several components. β2m was also undetected in the primary HCC lesions of the patients involved, indicating its in vivo relevance. We report for the first time HLA class I antigen loss with underlying B2M gene deficiency and APM defects in 50% (2 of 4) of the sHCC cell lines tested. These findings may have implications for a proper design of T cell immunotherapy for the treatment of sHCC patients.http://dx.doi.org/10.1155/2018/8363265 |
| spellingShingle | Wei-Yi Lei Shih-Chieh Hsiung Shao-Hsuan Wen Chin-Hsuan Hsieh Chien-Lin Chen Christopher Glenn Wallace Chien-Chung Chang Shuen-Kuei Liao Total HLA Class I Antigen Loss with the Downregulation of Antigen-Processing Machinery Components in Two Newly Established Sarcomatoid Hepatocellular Carcinoma Cell Lines Journal of Immunology Research |
| title | Total HLA Class I Antigen Loss with the Downregulation of Antigen-Processing Machinery Components in Two Newly Established Sarcomatoid Hepatocellular Carcinoma Cell Lines |
| title_full | Total HLA Class I Antigen Loss with the Downregulation of Antigen-Processing Machinery Components in Two Newly Established Sarcomatoid Hepatocellular Carcinoma Cell Lines |
| title_fullStr | Total HLA Class I Antigen Loss with the Downregulation of Antigen-Processing Machinery Components in Two Newly Established Sarcomatoid Hepatocellular Carcinoma Cell Lines |
| title_full_unstemmed | Total HLA Class I Antigen Loss with the Downregulation of Antigen-Processing Machinery Components in Two Newly Established Sarcomatoid Hepatocellular Carcinoma Cell Lines |
| title_short | Total HLA Class I Antigen Loss with the Downregulation of Antigen-Processing Machinery Components in Two Newly Established Sarcomatoid Hepatocellular Carcinoma Cell Lines |
| title_sort | total hla class i antigen loss with the downregulation of antigen processing machinery components in two newly established sarcomatoid hepatocellular carcinoma cell lines |
| url | http://dx.doi.org/10.1155/2018/8363265 |
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