Modulation of the HLA Peptidome of Cancer Cells by Cytokines

The human leukocyte antigen (HLA) class I presentation of peptide to T cells is a part of the immunosurveillance mechanism that enables the elimination of infected and diseased cells by the immune system. One of the hallmark of cancer is down-regulation of genes involved in the HLA class I expression such as TAP1/2 and LMP2/7. This is caused by the immunosuppressive tumor microenvironment and hinders immune response, thus contributing to the survival of the tumor cells. Interferons (IFNs) are a family of immune stimulatory cytokines, which up-regulates many components of the antigen presenting pathway, this way increasing both the quantity and the diversity of peptides presented by the HLA class I and therefore induce a strong immune response that can be directed against the cancer cells. The problem with the use of IFNs for cancer immune therapy relates to their high toxicity. Identifications of IFNs induced HLA peptides can be exploited to combine specific peptide immunization with low concentrations of IFNs treatment of cancer patients.

Our research strategy is based on treating human cancer cell lines with IFN-β or IFN-γ and characterizing the changes induced in the HLA class I peptidomes. Treating the cells with IFN-β and IFN-γ affected differently the cells’ proteome and HLA peptidome and induce the presentation of many unique HLA peptides. Therefore, treating the cells with the specific IFNs can trigger the HLA presentation of tumor specific antigens which are potential candidates for development of cancer vaccines.