| Abstract: |
Cancer testis (CT) antigens are attractive targets for immunotherapy in cancer patients. Immunohistochemistry was used to study the expression of the CT antigens MAGE-C2/CT-10, MAGE-C1/CT-7, GAGE, MAGE-A4 and NY-ESO-1 in 146 hepatocellular carcinomas, 13 intrahepatic cholangiocarcinomas, 37 extrahepatic cholangiocarcinomas and 32 gallbladder carcinomas. Immunopositivity was correlated with clinicopathological parameters, MHC Class 1 expression, intratumoral CD4<sub>+</sub>, CD8<sub>+</sub> and FOXP3<sub>+</sub> T cells and CD163<sub>+</sub> antigen-presenting cells. Of the 146 hepatocellular carcinomas, 34% were positive for MAGE-C2/CT-10,12% for MAGE-C1/CT-7,11% for GAGE and 2% for NY-ESO-1, respectively. MHC Class 1 coexpression was identified in almost all CT antigen-positive tumors. The number of intratumoral FOXP3 <sub>+</sub> regulatory T cells was increased in CT antigen-positive hepatocellular carcinomas (p < 0.004), suggesting inhibition of immune response in such tumors. Furthermore, MAGE-C1/CT-7 and GAGE positivity was correlated with reduced overall survival in patients with hepatocellular carcinoma (p = 0.03 and 0.01, respectively). Four (13%) gallbladder carcinomas stained positive for MAGE-C2/CT-10, of which 1 tumor (3%) was also positive for NY-ESO-1 and GAGE. CT antigens were not expressed in intra and extrahepatic cholangiocarcinomas. Our results suggest that MAGE-C2/CT-10 may be a good candidate for peptide vaccination in patients with hepatocellular carcinoma. © 2008 Wiley-Liss, Inc. |
| Keywords: |
immunohistochemistry; controlled study; unclassified drug; major clinical study; overall survival; hepatocellular carcinoma; advanced cancer; liver cell carcinoma; carcinoma, hepatocellular; liver neoplasms; transcription factor foxp3; antigen expression; cd8+ t lymphocyte; cd8-positive t-lymphocytes; forkhead transcription factors; metabolism; cancer immunotherapy; neoplasm proteins; cell line, tumor; tumor antigen; gene expression regulation; gene expression regulation, neoplastic; regulatory t lymphocyte; biosynthesis; immunotherapy; antigens, neoplasm; cancer testis antigen; ny eso 1 antigen; liver tumor; cancer immunization; cd4+ t lymphocyte; cd4-positive t-lymphocytes; tumor protein; tumor cell line; bile duct carcinoma; cholangiocarcinoma; antigens, cd; tissue microarray; gallbladder carcinoma; forkhead transcription factor; leukocyte antigen; antigen presenting cell; foxp3 protein, human; major histocompatibility antigen class 1; cancer testis gene; cancer vaccination; cd163 antigen; ct 10 antigen; ct 7 antigen; gage antigen; mage c1 antigen; mage c2 antigen; melanoma antigen 4; cell surface receptor; differentiation antigen; magec2 protein, human; antigens, differentiation, myelomonocytic; receptors, cell surface
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