title: MUC1 immunotherapy against a metastatic mammary adenocarcinoma model: Importance of IFN-gamma.
abstract: Immunotherapy using mucin 1 (MUC1) linked to oxidised mannan (MFP) was investigated in an aggressive MUC1+ metastatic tumour, DA3-MUC1 because, unlike many MUC1+ tumour models, DA3-MUC1 is not spontaneously rejected in mice making it an alternative model for immunotherapy studies. Further, DA3-MUC1 cells are resistant to lysis by anti-MUC1 cytotoxic T cells (CTLs). The inability of DA3-MUC1 tumours to be rejected in naïve mice as well as vaccination to MUC1 was attributed to a deficiency of expression of MHC class I molecules on the tumour cell surface. In vitro and in vivo analysis of subcutaneous tumours and lung metastases demonstrated that DA3-MUC1 tumour cells have a low expression (< 6%) of MHC class I which can be upregulated (> 90%) following culturing with IFN-γ. Results from flow cytometry analysis and immunoperoxidase staining indicated that the in vitro up-regulation of MHC class I could be maintained for up to seven days in vivo, without affecting the expression levels of MUC1 antigen. Interestingly, MUC1-specific CTL that lyse DA3-MUC1 targets in vitro were induced in MFP immunised mice but failed to protect mice from a DA3-MUC1 tumour challenge. These results highlight the importance of MHC class I molecules in the induction of anti-tumour immunity and the MFP immune response.
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Lees
authors.forename: Nechama
authors.initials: N
authors.lastname: Smorodinsky
authors.forename: Galit
authors.initials: G
authors.lastname: Horn
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Wreschner
authors.forename: Ian F C
authors.initials: IF
authors.lastname: McKenzie
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Pietersz
authors.forename: Lily
authors.initials: L
authors.lastname: Stojanovska
authors.forename: Vasso
authors.initials: V
authors.lastname: Apostolopoulos
mesh_terms: D000230:Adenocarcinoma / Q000209:etiology* / Q000556:secondary*; D000818:Animals; D001943:Breast Neoplasms / Q000209:etiology / Q000473:pathology*; D005260:Female; D015395:Histocompatibility Antigens Class I; D007167:Immunotherapy; D007371:Interferon-gamma / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018396:Mucin-1 / Q000276:immunology*
chemical_list: D015395:Histocompatibility Antigens Class I; D018396:Mucin-1; D007371:Interferon-gamma