Pancreatic ductal adenocarcinoma (PDAC) has a dismal 5-year survival rate of only 10% in the United States. While immune checkpoint blockade (ICB) has shown efficacy in many solid tumors, PDAC remains largely unresponsive. Agonistic CD40 antibodies can activate PDAC-associated myeloid cells, enhancing innate and adaptive anti-tumor immunity. However, clinical trials with agonistic CD40 antibodies have demonstrated only modest efficacy and significant hepatotoxicity. We previously reported that IL-1 pathway blockade enhances CD40 agonist efficacy against melanoma by depleting polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs
CD11b