Total HLA Class I Antigen Loss with the Downregulation of Antigen-Processing Machinery Components in Two Newly Established Sarcomatoid Hepatocellular Carcinoma Cell Lines
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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 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 -microglobulin ( m) and marked HLA class I heavy chain and selective antigen-processing machinery (APM) component downregulation. The loss of m in sHCC29 and sHCC63 was caused by a >49 kb deletion across the locus, while their downregulation of APM components was transcriptional, reversible by IFN- only in several components. m was also undetected in the primary HCC lesions of the patients involved, indicating its relevance. We report for the first time HLA class I antigen loss with underlying 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.
Wang W, Li Y, Ko S, Feng N, Zhang M, Liu J bioRxiv. 2024; .
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Sverchkova A, Burkholz S, Rubsamen R, Stratford R, Clancy T BMC Med Genomics. 2024; 17(1):37.
PMID: 38281021 PMC: 10821267. DOI: 10.1186/s12920-024-01808-8.
Gama-Cuellar A, Diaz K, Calleja M, Saavedra G, Ramirez-Amador V, Corro J Med Oral Patol Oral Cir Bucal. 2023; 29(2):e273-e279.
PMID: 37992142 PMC: 10945878. DOI: 10.4317/medoral.26248.
Liu Q, Tian Y, Li Y, Zhang W, Cai W, Liu Y J Immunother Cancer. 2020; 8(2).
PMID: 33323464 PMC: 7745518. DOI: 10.1136/jitc-2020-001748.