Expression of class I and class II major histocompatibility antigens on human hepatocellular carcinoma.

Sung, Chiu-Mei; Hu, Cheng; Hsu, Hey‐Chi; Ng, Ah Kau; Chou, Chen‐Kung; Ting, Ling-Pai; Su, Tung-Hung; Han, Shou‐Hwa; Chang, Chung-Ming

doi:10.1172/jci113900

Cited by 33 publications

(29 citation statements)

References 39 publications

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“…Several studies have shown that HLA-DR protein can be expressed by HCC cells; however, its relation to metastatic potential has not been discussed. 21,22 HLA-DR protein is involved in the antigen presenting function of macrophages including dendritic cells. 22 Activated lymphocytes also express the HLA-DR antigen.…”

Section: Discussionmentioning

confidence: 99%

Tumor HLA‐DR expression linked to early intrahepatic recurrence of hepatocellular carcinoma

Matoba

Iizuka

Gondo

et al. 2005

Intl Journal of Cancer

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The outcome of patients with hepatocellular carcinoma (HCC) remains poor because of the high frequency of intrahepatic recurrence (IHR), particularly early IHR within 1 year of hepatectomy. To search for genes involved in early IHR, we performed DNA microarray analysis in a training set of 33 HCCs and selected 46 genes linked to early IHR from approximately 6,000 genes by means of a supervised learning method. Gene selection was validated by a false discovery rate of 0.37%. The 46 genes included many immune response-related genes, which were all downregulated in HCCs with early IHR. Four of these genes (HLA-DRA, HLA-DRB1, HLA-DG and HLA-DQA), encoding MHC class II antigens, were coordinately downregulated in HCCs with early IHR compared to levels in HCCs with nonrecurrence. A cluster analysis reproduced expression patterns of the 4 MHC class II genes in 27 blinded HCC samples. To localize the major site of production of HLA-DR protein in the tumor, we used 50 frozen specimens from 50 HCCs. Immunofluorescence staining showed that HLA-DR protein levels in tumor cells, but not in stromal cells, were associated with the transcription levels of HLA-DRA determined by both DNA microarray analysis and real-time quantitative reverse transcription-PCR. Univariate analysis showed that tumor HLA-DR protein expression, pTNM stage and venous invasion were associated with early IHR. Multivariate analysis showed that tumor HLA-DR protein expression was one of the independent risk factors for early IHR, suggesting HLA-DR protein potential as a biomarker and a molecular target for therapeutic intervention. ' 2005 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 99%

Tumor HLA‐DR expression linked to early intrahepatic recurrence of hepatocellular carcinoma

Matoba

Iizuka

Gondo

et al. 2005

Intl Journal of Cancer

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“…These include hepatitis B virus infection [3][4][5] and hepatoceilular carcinoma {HCC) [2,[5][6][7]. Paterson et al [2] have reported a homogeneous acquisition or enchancement of MHC class I with concomitant expression ofthe invariant chain, /'^2-microglobulin {/32-M).…”

Section: Introductionmentioning

confidence: 99%

“…These may be useful tools for (he study of MHC gene expression and regulation in hepatocytes as well as for the investigation of MHC antigens with transformation of human hepatocytes [5,7,8]. Most antigens, although results have sometimes been at odds [9,10].…”

Section: Introductionmentioning

confidence: 99%

HLA expression in hepatocellular carcinoma cell lines

Wadee

Paterson

Coplan

et al. 1994

Clinical and Experimental Immunology

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SUMMARYThe present study undertook to investigate the biological significance of human leucocyte antigen expression in hepatoceilular carcinoma and to elucidate lhc role of potential modulating agents on human leucocyte antigen expression. These studies used several hepatic tumour-derived cell lines as in vitro model systems. The cell lines included PLC/PRF/5 (Alexander cell line), Hep3B. HepG2, TONG PHC, HA22T/VGH, HA59T/VGH and Mahlavu, The cell lines K562 and Raji were used as negative and positive controls, respectively. K562, a B tymphoid-derived cell line, was shown to express negligible amounts of human leucocyte anligens, while Raji, an erythromyeloid-derived cell line, expressed both class I and class II human leucocyte anligens as well as their respective invariant chains, ^2-niicroglobulin and Ii. Using an ELISA, experiments performed on these cell lines confirmed the natural expression of class I and class II antigens by the HA22T/VGH and HA59T/VGH cell lines, whereas PLC/PRF/5 displayed class II surface antigens only. The effects of modulating agents such as interferon-gamma sodium bulyrate and clofazimine on human leucocyte antigen expression were investigated using the HA22T/VGH, HA59T/VGH and TONG PHC cell lines. These agents increased class 1 and class II human leucocyte antigen expression on HA22T/VGH and TONG PHC cells, but had no effect on the HA59T/VGH cell line. The results suggest a potential use for these agents as modulators of human leucocyte antigen expression by human heptocellular cell lines.

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“…Previous studies of MHC expression on human hepatocytes or hepatoma cells were mostly assessed with immunohistochemistry, radioimmunobinding assay or ELISA (Sung et al, 1989;Wadee et al, 1994). Recently, flow cytofluorimetry has been widely used to investigate the antigens expressed on the cell surface of target cells, not only because of its high sensitivity but also of its quantifiability (Anderson et al, 1993;Vidovic et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

“…The expression of MHC antigens on human hepatoma cell lines and liver tissues has been reported (Sung et al, 1989;Wadee et al, 1994), and the loss or decrease of MHC class I antigens has been demonstrated in some hepatoma cell lines (Kurokohchi et al, 1996). bated at 37°C in a C02 incubator with 5% C0 2 -Monoclonal antibody (MAb) L243, against the DR region of MHC class II antigens (M090-7360, Becton Dickinson Immunocytometry Systems.…”

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confidence: 99%

Cordyceps sinensisIncreases the Expression of Major Histocompatibility Complex Class II Antigens on Human Hepatoma Cell Line HA22T/VGH Cells

Chiu

Wu³

et al. 1998

Am. J. Chin. Med.

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Previous studies suggest that down-regulation of the major histocompatibility complex (MHC) antigens on the cell surface of certain tumors results in an escape of immune surveillance. Cordyceps sinensis is well known for its modulatory effect on host immune system. To investigate the modulatory effect of Cordyceps sinensis on MHC class II antigen expression on hepatoma cells, immunostaining with monoclonal antibody (MAb) L243, against the HLA DR region of MHC class II antigens on human hepatoma cell line HA22T/VGH was analyzed by using flow cytofluorimetry. The degree of fluorescence intensity on L243(+) cells was expressed as relative mean fluorescence intensity (RMFI). The extract of Cordyceps sinensis (VGH-CS-ME-82, 40 micrograms/ml) was found to increase the MHC class II antigen expression on HA22T/VGH cells with the percentage of L243(+) cells 40.2 +/- 2.5 and RMFI 6.6 +/- 0.4; whereas cells without treatment disclosed the percentage of L243(+) cells 17.2 +/- 1.4 and RMFI 5.4 +/- 0.3, respectively (p < 0.05). There was a dose-related increase in the degree of fluorescence intensity in terms of RMFI on VGH-CS-ME-82 induced cells. The RMFI in cells treated with IFN-gamma 0, 0.2 and 5 ng/ml were 5.4 +/- 0.3, 8.2 +/- 0.4, and 24.9 +/- 1.5, respectively; whereas the RMFI in cells co-incubated with VGH-CS-ME-82 (40 micrograms/ml) and IFN-gamma 0, 0.2 ng/ml and 5 ng/ml were 6.7 +/- 0.2 (p < 0.05), 9.2 +/- 0.9 (p < 0.1) and 29.5 +/- 1.2 (p < 0.005), respectively. We conclude that VGH-CS-ME-82, either alone or with IFN-gamma induction, increases the MHC class II antigen expression on hepatoma cell line HA22T/VGH, which will shed light into the present immunotherapy, and make the host immune surveillance more effective against tumor cells with down-regulated MHC class II antigen expression.

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Expression of class I and class II major histocompatibility antigens on human hepatocellular carcinoma.

Cited by 33 publications

References 39 publications

Tumor HLA‐DR expression linked to early intrahepatic recurrence of hepatocellular carcinoma

Tumor HLA‐DR expression linked to early intrahepatic recurrence of hepatocellular carcinoma

HLA expression in hepatocellular carcinoma cell lines

Cordyceps sinensisIncreases the Expression of Major Histocompatibility Complex Class II Antigens on Human Hepatoma Cell Line HA22T/VGH Cells

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