CIITA versus IFN-gamma induced MHC class II expression in head and neck cancer cells.
A growing body of evidence suggests that optimal induction of systemic anti-tumor immunity requires priming of both the CD4+ and CD8+ T cells that are specific for tumor-associated antigens (TAA). Recently, it was shown that MHC class II positive tumor cells are able to induce tumor-specific CD4+ T cells, and that this event may improve clinical outcome. This has rekindled the interest in modulating MHC class II expression in nonprofessional antigen presenting tumor cells. The class II transactivator (CIITA) is a major regulator of MHC class I and class II expression. We compared, in head and neck cancer cell lines, the effect of stable overexpression of CIITA to treatment with IFN-gamma on the cell surface expression profile of MHC class I and II molecules. Here, we provide evidence that CIITA transfection is more effective than IFN-gamma in inducing MHC class II expression. To more thoroughly explore the mechanisms of MHC class II induction in this context, we used RT-PCR to measure the mRNA expression pattern of HLA-DR, HLA-DM, cathepsin S, and the invariant chain. In contrast to the effect of treatment with IFN-gamma, CIITA transfection did not induce cathepsin S, an important protease responsible for the degradation of the invariant chain, and thus for binding of the peptides to the MHC class II binding groove. These findings may have a significant impact on practical and clinical aspects of tumor immunotherapeutic strategies.
Meissner
Markus
M
Department of Dermatology, Johann Wolfgang Goethe-University, 60590 Frankfurt, Germany. markus.meissner@kgu.de
Whiteside
Theresa L
TL
Kaufmann
Roland
R
Seliger
Barbara
B
D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000276:immunology*; D002403:Cathepsins / Q000378:metabolism; D045744:Cell Line, Tumor; D005802:Genes, MHC Class II / Q000502:physiology*; D006681:HLA-D Antigens / Q000378:metabolism; D006684:HLA-DR Antigens / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D006681:HLA-D Antigens; C084245:HLA-DM antigens; D006684:HLA-DR Antigens; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D007371:Interferon-gamma; D002403:Cathepsins; C028217:cathepsin S