title: On the biological relevance of MHC class II and B7 expression by tumour cells in melanoma metastases.
abstract: A large number of studies have indicated that specific immune reactivity plays a crucial role in the control of malignant melanoma. In this context, expression of MHC I, MHC II and B7 molecules by melanoma cells is seen as relevant for the immune response against the tumour. For a better understanding of the biological relevance of MHC II and B7 expression by tumour cells in metastatic melanoma, we studied the expression of these molecules in melanoma metastases in relation to the inflammatory response, regression of the tumour and survival from 27 patients treated with biochemotherapy (30 mg m(-2) Cisplatin and 250 mg m(-2) decarbazine (dimethyl-triazene-imidazole-carboxamide, DTIC) on days 1-3 i.v., and 10(7) IU IFN-alpha 2b 3 days a week s.c., q. 28d). In 19 out of 27 lesions studied, we found expression of MHC II by the tumour cells, while only in one out of 11 tumour biopsies obtained from untreated metastatic melanoma patients, MHC II expression was detected. Expression of B7.1 and B7.2 by tumour cells was found in nine out of 24 and 19 out of 24 lesions, respectively. In all cases where B7.1 expression was found, expression of B7.2 by the tumour cells was also seen. In general, no or only few inflammatory cells positive for B7 were found. Expression of MHC II by tumour cells was positively correlated with the presence of tumour-infiltrating lymphocytes, regression of the lesion, and with time to progression (TTP) and overall survival (OS) of the patient. However, no significant correlation between B7.1 or B7.2 expression and regression of the tumour, TTP or OS was found. In light of other recent findings, these data altogether do support a role as biomarker for MHC II expression by tumour cells; however, its exact immunological pathomechanism(s) remain to be established.
authors.affiliation: Division of Clinical Tumour Immunology, Department of Oncology, University Hospital, Linköping, Sweden. m.bernsen@pathol.azn.nl
authors.forename: M R
authors.initials: MR
authors.lastname: Bernsen
authors.forename: L
authors.initials: L
authors.lastname: Håkansson
authors.forename: B
authors.initials: B
authors.lastname: Gustafsson
authors.forename: L
authors.initials: L
authors.lastname: Krysander
authors.forename: B
authors.initials: B
authors.lastname: Rettrup
authors.forename: D
authors.initials: D
authors.lastname: Ruiter
authors.forename: A
authors.initials: A
authors.lastname: Håkansson
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis; D018122:B7-1 Antigen / Q000096:biosynthesis*; D051940:B7-2 Antigen; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis*; D006801:Humans; D008297:Male; D008545:Melanoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000556:secondary; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016019:Survival Analysis
chemical_list: D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D008562:Membrane Glycoproteins