TY - JOUR T1 - Inflammasome- and gasdermin D-independent IL-1β production mobilizes neutrophils to inhibit antitumor immunity JF - bioRxiv DO - 10.1101/2020.08.04.235796 SP - 2020.08.04.235796 AU - Máté Kiss AU - Lieselotte Vande Walle AU - Els Lebegge AU - Helena Van Damme AU - Aleksandar Murgaski AU - Junbin Qian AU - Manuel Ehling AU - Samantha Pretto AU - Evangelia Bolli AU - Jiri Keirsse AU - Yvon Elkrim AU - Maria Solange Martins AU - Amelie Fossoul AU - Diether Lambrechts AU - Massimiliano Mazzone AU - Andy Wullaert AU - Mohamed Lamkanfi AU - Jo A. Van Ginderachter AU - Damya Laoui Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/08/04/2020.08.04.235796.abstract N2 - Interleukin-1β (IL-1β) is a central mediator of inflammation whose secretion typically requires proteolytic maturation by the inflammasome and formation of membrane pores by gasdermin D (GSDMD). Emerging evidence suggests an important role for IL-1β in promoting cancer progression in patients, but the underlying mechanisms are little understood. Here, we show a key role for IL-1β in driving tumor progression in two distinct mouse tumor models. Notably, inflammasome activation and GSDMD were dispensable for the production of intratumoral bioactive IL-1β, which promoted systemic mobilization and infiltration of neutrophils into tumors. Neutrophils recruited via IL-1β suppressed the acquisition of an effector T-cell phenotype and subsequent antitumor immune response. Moreover, IL-1β was essential for neutrophil accumulation upon antiangiogenic therapy, thereby contributing to therapy-induced immunosuppression. Antitumor immunity in the absence of IL-1β-dependent neutrophil recruitment relied on immunostimulatory macrophages which promoted the infiltration and activation of cytotoxic T-cells. Overall, these results support a tumor-promoting role for IL-1β through establishing an immunosuppressive microenvironment and show that inflammasome activation is not essential for its release in tumors.Competing Interest StatementThe authors have declared no competing interest. ER -