PO-403 The tumour suppressor P53 as a guardian of immune tolerance and suppression

Introduction Pancreatic cancer is one of the poorest understood cancers with a in vivo. A model of pancreatic ductal adenocarcinoma (PDAC) was generated using a Cre-recombinase system with the following combinations KRas G12D ;p53 +/+ or KRas G12D ;p53 f/f . Using a technique of tumour rejection, we demonstrate a role for p53 in PDAC cells in modulating the immune response. Material and methods In vivo studies were done using PDAC cell lines derived from GEMMs with ectopic expression of iRFP. FVB or CD1 nu/nu mice were injected subcutaneously with PDAC lines and subcutaneous growth was measured using the Licor Pearl Imager. Immunophenotyping was performed using flow cytometry (i.e. intracellular cytokine staining and surface staining) and acquired on the BD Symphony Fortessa. In vitro studies were conducted on the PDAC cell lines, bone marrow derived macrophages (BMDM) and primary T cells. Results and discussions Genetic ablation of p53 in PDAC cells provided immunological advantage and delayed tumour rejection. Immunophenotyping results demonstrated a suppression of Th1-like responses in vivo as well as changes in myeloid populations. In vitro studies provided evidence of alterations in macrophage priming and consequential changes in T cell polarisation. Recent studies have demonstrated roles for oncogenes, such as c-Myc and KRas in influencing anti-tumourgenic responses, which supports our data of p53-dependent changes. Conclusion Over the last 50 years immunoediting of the tumour has been shown to be a powerful mechanism of a tumour selection. Loss and mutation of p53 occurs quite frequently in human cancers and understanding the underlying immunological mechanisms of escape in the context of p53 is crucial in developing immunotherapies.