Abstract 102: Ferrichrome suppresses pancreatic tumor growth via targeting TAMs and enhancing CD8+ T-cells infiltration

Background: Pancreatic cancer (PanCa) is one of the most lethal malignancy with a very poor survival rate in patients due to inadequate treatment options. Accumulating evidences suggest that tumor associated macrophages (TAMs) and reduce infiltration of CD8+ T-cell population provide tumor suppressive environment leading to advanced growth and metastasis of PanCa. Thus, targeting TAMs and enhancing infiltration of CD8+ T-cells to the tumor site by non-toxic agents could be an effective therapeutic approach for the management of PanCa. In this study, we demonstrate that a novel probiotic-derived agent (ferrichrome) inhibits pancreatic tumor growth in syngeneic mouse model via modulating TAMs and increasing infiltration of CD8+ T-cells. Methods: RAW264.7 cells, murine peritoneal macrophages, mouse pancreatic cancer cells (UN-KC-6141) were used for this study. Effect of ferrichrome on the expression of pro (IL-12, p40, iNOS, IL-6), anti-inflammatory cytokines (MRC1 and Arginase-1) and iron metabolism markers (ferritin and ferroportin) in macrophages and co-culture systems was analyzed by qPCR. Effect of ferrichrome on metastatic phenotypes of PanCa cells was analyzed in a co-culture model of RAW264.7 and UN-KC-6141 cells. Therapeutic efficacy of ferrichrome was determined in syngeneic mouse model. Tumor immune infiltrating cells were analyzed in excised tumors by FACS, double immunofluorescence and immunohistochemistry analyses. Results: Ferrichrome treatment reversed the polarization of M2 macrophages towards the M1 phenotype as observed by increase expression of IL-12p40, iNOS, IL-6 and decrease expression of MRC1 and Arginase-1. Ferrichrome significantly (P