MUC1 immunotherapy against a metastatic mammary adenocarcinoma model: Importance of IFN-gamma

Catherine J. Lees, Nechama Smorodinsky, Galit Horn, Daniel H. Wreschner, Ian F.C. McKenzie, Geoffrey Pietersz, Lily Stojanovska, Vasso Apostolopoulos

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)15-25
Number of pages11
JournalPrilozi (Makedonska akademija na naukite i umetnostite. Oddelenie za medicinski nauki)
Volume37
Issue number1
DOIs
Publication statusPublished - Jan 1 2016
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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