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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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Autores principales: Lei, Wei-Yi, Hsiung, Shih-Chieh, Wen, Shao-Hsuan, Hsieh, Chin-Hsuan, Chen, Chien-Lin, Wallace, Christopher Glenn, Chang, Chien-Chung, Liao, Shuen-Kuei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6311956/
https://www.ncbi.nlm.nih.gov/pubmed/30648121
http://dx.doi.org/10.1155/2018/8363265
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author Lei, Wei-Yi
Hsiung, Shih-Chieh
Wen, Shao-Hsuan
Hsieh, Chin-Hsuan
Chen, Chien-Lin
Wallace, Christopher Glenn
Chang, Chien-Chung
Liao, Shuen-Kuei
author_facet Lei, Wei-Yi
Hsiung, Shih-Chieh
Wen, Shao-Hsuan
Hsieh, Chin-Hsuan
Chen, Chien-Lin
Wallace, Christopher Glenn
Chang, Chien-Chung
Liao, Shuen-Kuei
author_sort Lei, Wei-Yi
collection PubMed
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 β (2)-microglobulin (β (2)m) and marked HLA class I heavy chain and selective antigen-processing machinery (APM) component downregulation. The loss of β (2)m 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. β (2)m 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.
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spelling pubmed-63119562019-01-15 Total HLA Class I Antigen Loss with the Downregulation of Antigen-Processing Machinery Components in Two Newly Established Sarcomatoid Hepatocellular Carcinoma Cell Lines Lei, Wei-Yi Hsiung, Shih-Chieh Wen, Shao-Hsuan Hsieh, Chin-Hsuan Chen, Chien-Lin Wallace, Christopher Glenn Chang, Chien-Chung Liao, Shuen-Kuei J Immunol Res Research Article 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 β (2)-microglobulin (β (2)m) and marked HLA class I heavy chain and selective antigen-processing machinery (APM) component downregulation. The loss of β (2)m 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. β (2)m 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. Hindawi 2018-12-16 /pmc/articles/PMC6311956/ /pubmed/30648121 http://dx.doi.org/10.1155/2018/8363265 Text en Copyright © 2018 Wei-Yi Lei et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Lei, Wei-Yi
Hsiung, Shih-Chieh
Wen, Shao-Hsuan
Hsieh, Chin-Hsuan
Chen, Chien-Lin
Wallace, Christopher Glenn
Chang, Chien-Chung
Liao, Shuen-Kuei
Total HLA Class I Antigen Loss with the Downregulation of Antigen-Processing Machinery Components in Two Newly Established Sarcomatoid Hepatocellular Carcinoma Cell Lines
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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6311956/
https://www.ncbi.nlm.nih.gov/pubmed/30648121
http://dx.doi.org/10.1155/2018/8363265
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