Friday, May 3, 2024
5/3/2024
Abstract The MYC oncogene is a common cause of human cancers and the presence of MYC alterations is associated with poor prognosis for hematological malignancies. To date, there are no FDA approved MYC specific drugs and this is an area of active research. Our laboratory is focused on understanding how MYC causes cancer and identifying genes and pathways that can be targeted to treat cancer. There is now a wealth of evidence indicating that MYC suppresses the immune system during tumor development and experimental inactivation of MYC relieves this suppression resulting in an anti-cancer immune response. While we have mechanistic insight into how MYC regulates CD4+ T-cells, NK cells and macrophages, it is still not know whether MYC also influences B-cell immunity. This fact is suggested by our preliminary data which indicates that experimental shut off of MYC results in an enhanced serum IgG antibody response that appears to be tumor specific. This begs the question of how exactly B-cell responses are altered in the presence of MYC activation, what antigens are being recognized and what impact do serum antibodies and B-cells have on disease regression following MYC inactivation. We hypothesize that that MYC inactivation leads to a change in the B-cell MHC class II peptide repertoire altering the type and spectrum of antigens presented and contributing to increased tumor immunogenicity. We will use a well described model of MYC-driven T-cell acute lymphoblastic lymphoma (hMYC T-ALL) to address the following two aims: AIM 1) Interrogate the role of MYC on regulating the B-cell MHC II antigen processing machinery and AIM 2) defining the influence of MYC on the B-cell MHC class II peptide repertoire. It is our hope that this study will identify new antigenic targets and antibodies that will form the basis of future therapies and additional lines of inquiry.
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