059 Enhanced and suppressed tumor immunity is mediated by IL-1R1 on distinct immune cells

Inflammation is necessary for immune defense against pathogens and a functional antitumor response, but chronic inflammation promotes tumor growth enables tumors to escape from immune-mediated destruction. Recently, we others demonstrated that deficiency of IL1β strongly favors immunity, multiple clinical trials involving antibody mediated blockade in cancers are underway. The mechanism, however, remains obscure. We intact IL1α signaling was required blockade-induced leading the hypothesis its interaction with IL1 type I receptor (IL1R1) subsequent response. To determine which cell signal, studied response several mouse lines where IL1R1 conditionally deleted T cells (LckCre), dendritic (CD11cCre), or macrophages (LysMCre) on an IL1β-sufficient -deficient background. When absent compartment augmented control MC38.OVA IL1β-deficient mice lost. This indicated through enabled observed anti-tumor contribution other cells, measured IL1R monocytes/macrophages. did not observe difference when IL-1R cells. Strikingly, conditional deletion monocytes/macrophages further delayed compared already significant inhibition mice. Since both only signal IL-1R, propose costimulation provokes immunity; this antagonized by activation (predominantly IL1β), suppression immunity MDSC macrophages. Understanding complexity may help optimize blocking therapy immunity.