title: HLA-G and classical HLA class I expression in primary colorectal cancer and associated liver metastases.
abstract: De novo expression of HLA-G has been demonstrated in colorectal cancer. HLA-G, amongst others, inhibits natural killer cell function, contributing to host immune defense evasion. Another mechanism to escape anti-tumor immunity is loss of HLA class I. Therefore, we determined HLA-G and HLA class I expression on primary colorectal tumors and associated liver metastases, in order to get insight in the metastasizing process regarding escaping anti-tumor immunity. HLA-G expression was evaluated using three mAbs; 4H84, MEM-G/1 and MEM-G/2. In total 81 colorectal cancer patients were evaluated. Formalin-fixed paraffin-embedded tissue sections of primary tumors and associated liver metastases, were immunohistochemically stained. A concordance between expression or loss/downregulation in the primary tumor and associated liver metastasis regarding HLA class I expression was observed in 80% of the cases. In contrast with the hypothesis of escaping NK cell-killing, we demonstrated for each HLA-G detecting mAbs used in this study, that the majority of the primary tumors that positively stained for HLA-G did not express HLA-G in the associated liver metastasis. Furthermore, we revealed the existence of non-specific binding and in addition we found that the different epitopes of HLA-G detected by 4H84, MEM-G/1 and MEM-G/2 mAbs were expressed differentially in colorectal tumor tissues.
authors.affiliation: Dept. of Surgery, Leiden University Medical Center, Leiden, The Netherlands; Dept. of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Marloes
authors.initials: M
authors.lastname: Swets
authors.affiliation: Dept. of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Marion H
authors.initials: MH
authors.lastname: König
authors.affiliation: Dept. of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Anniek
authors.initials: A
authors.lastname: Zaalberg
authors.affiliation: Dept. of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Neeltje G
authors.initials: NG
authors.lastname: Dekker-Ensink
authors.affiliation: Dept. of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: Gelderblom
authors.affiliation: Dept. of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Cornelis J H
authors.initials: CJ
authors.lastname: van de Velde
authors.affiliation: Dept. of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands; Dept. of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: van den Elsen
authors.affiliation: Dept. of Surgery, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: P.J.K.Kuppen@lumc.nl.
authors.forename: Peter J K
authors.initials: PJ
authors.lastname: Kuppen
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000378:metabolism; D003106:Colon / Q000378:metabolism* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D000939:Epitopes / Q000378:metabolism*; D005260:Female; D059951:HLA-G Antigens / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007694:Killer Cells, Natural / Q000276:immunology; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism* / Q000556:secondary; D008297:Male; D008875:Middle Aged
chemical_list: D000911:Antibodies, Monoclonal; D000939:Epitopes; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I
keywords: Colorectal cancer; HLA class I; HLA-G; Liver metastases