159 IL-1R1 on distinct immune cells can strongly enhance or inhibit tumor immunity

Inflammation is necessary for defense against pathogens, but chronic inflammation can promote tumor growth and enable tumors to escape from immune-mediated destruction. Recently, we demonstrated that deficiency of IL1β favors antitumor immunity, multiple clinical trials involving antibody mediated blockade in cancers are underway. We showed IL1α signaling was required blockade-induced leading the hypothesis its interaction with IL1 type I receptor (IL1R1) immune 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 -sufficient -deficient background. When absent compartment augmented control MC38.OVA mice lost. This indicated through enabled anti-tumor Deletion IL-1R DC had no effect. contribution other cells, measured IL1R monocytes/macrophages. Strikingly, conditional deletion monocytes/ further delayed beyond substantial inhibition IL1β-deficient mice. also corresponded increase XCR1+ cDC1 cells. Given vivo injection inflammatory process, expanded our study autochthonous BRafCA/+/PTENloxp/ R26EGFPOVA/Tyr;;CreERT2 (BPO) model IL1β–/– In BPO/IL1β–/– fewer CD8 TILs expressed PD-1 (20.1±1.9 vs. 9.3±1.0 S.E.M.), correlated EGFP-OVA+tumor propose costimulation promotes this strongly antagonized by activation monocytes/macrophages IL1β, suppression MDSC macrophages. Manipulating balance may help optimize IL-1b blocking therapy immunity.