PT - JOURNAL ARTICLE AU - Dyevoich, Allison M AU - Haas, Karen M TI - Type I IFN, Ly6C+ cells, and phagocytes support suppression of peritoneal carcinomatosis elicited by a TLR and CLR agonist combination AID - 10.1158/1535-7163.MCT-19-0885 DP - 2020 Jan 01 TA - Molecular Cancer Therapeutics PG - molcanther.0885.2019 4099 - http://mct.aacrjournals.org/content/early/2020/03/18/1535-7163.MCT-19-0885.short 4100 - http://mct.aacrjournals.org/content/early/2020/03/18/1535-7163.MCT-19-0885.full AB - Metastatic cancer involving spread to the peritoneal cavity is referred to as peritoneal carcinomatosis and has a very poor prognosis. Our previous study demonstrated a toll-like receptor (TLR) and C-type lectin receptor (CLR) agonist pairing of monophosphoryl lipid A (MPL) and trehalose-6,6'-dicorynomycolate (TDCM) effectively inhibits tumor growth and ascites development following TA3-Ha and EL4 challenge through a mechanism dependent upon B-1a cell-produced natural IgM and complement. In the current study, we investigated additional players in the MPL/TDCM-elicited response. MPL/TDCM treatment rapidly increased type I IFN levels in the peritoneal cavity along with myeloid cell numbers, including macrophages and Ly6Chi monocytes. Type I IFN receptor (IFNAR1-/-) mice produced tumor-reactive IgM following MPL/TDCM treatment, but failed to recruit Ly6C+ monocytes and were not afforded protection during tumor challenges. Clodronate liposome depletion of phagocytic cells, as well as targeted depletion of Ly6C+ cells, also ablated MPL/TDCM-induced protection. Cytotoxic mediators known to be produced by these cells were required for effects. TNFa was required for effective TA3-Ha killing and nitric oxide was required for EL4 killing. Collectively, these data reveal a model whereby MPL/TDCM-elicited anti-tumor effects strongly depend on innate cell responses, with B-1a cell-produced tumor-reactive IgM and complement pairing with myeloid cell-produced cytotoxic mediators to effectively eradicate tumors in the peritoneal cavity.