title: Favorable outcome in clinically stage II melanoma patients is associated with the presence of activated tumor infiltrating T-lymphocytes and preserved MHC class I antigen expression.
abstract: In this study we investigated whether the presence of specific populations of tumor infiltrating lymphocytes (TILs) in diagnostic primary melanoma biopsies are related to outcome in clinically stage II melanoma patients. Moreover, we investigated whether the presence of TILs correlates with expression of MHC class I antigen and MHC class II antigen on tumor cells and/or tumor infiltrating antigen presenting cells. Diagnostic primary melanoma samples of 15 patients with an unfavorable outcome were compared with 20 patients with favorable outcome. Patients were matched for age, gender and Breslow thickness. Biopsies were examined for the presence of granzyme B+, CD8+, CD4+ and CD56+ TILs and for expression of MHC class I antigen and MHC class II antigen on tumor and/or tumor infiltrating cells. A favorable clinical outcome was strongly associated with the presence of GrB+ and CD4+ TILs, with expression of MHC class I antigen on tumor cells and with expression of MHC class II antigen on intratumoral antigen presenting cells. These data strongly support the notion that in melanoma patients the cellular immune response is a major factor in preventing melanoma cell dissemination.
authors.affiliation: Department of Pathology, VU Medical Center, de Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
authors.forename: Inge S
authors.initials: IS
authors.lastname: van Houdt
authors.forename: Berbel J R
authors.initials: BJ
authors.lastname: Sluijter
authors.forename: Laura M
authors.initials: LM
authors.lastname: Moesbergen
authors.forename: Wim M
authors.initials: WM
authors.lastname: Vos
authors.forename: Tanja D
authors.initials: TD
authors.lastname: de Gruijl
authors.forename: Barbara G
authors.initials: BG
authors.lastname: Molenkamp
authors.forename: Alfons J M
authors.initials: AJ
authors.lastname: van den Eertwegh
authors.forename: Erik
authors.initials: E
authors.lastname: Hooijberg
authors.forename: Paul A M
authors.initials: PA
authors.lastname: van Leeuwen
authors.forename: Chris J L M
authors.initials: CJ
authors.lastname: Meijer
authors.forename: Joost J
authors.initials: JJ
authors.lastname: Oudejans
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000938:Antigen-Presenting Cells / Q000276:immunology; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D015704:CD4 Antigens / Q000032:analysis; D019002:CD56 Antigen / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D005260:Female; D053804:Granzymes / Q000032:analysis; D015395:Histocompatibility Antigens Class I / Q000032:analysis*; D000949:Histocompatibility Antigens Class II / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008213:Lymphocyte Activation; D016246:Lymphocytes, Tumor-Infiltrating; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000473:pathology*; D008875:Middle Aged; D009367:Neoplasm Staging; D012878:Skin Neoplasms / Q000276:immunology* / Q000473:pathology*; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D015704:CD4 Antigens; D019002:CD56 Antigen; D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D053804:Granzymes