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Inflammasome- and gasdermin D-independent IL-1β production mobilizes neutrophils to inhibit antitumor immunity
Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2020.08.04.235796v1?rss=1
Authors: Kiss, M., Vande Walle, L., Lebegge, E., Van Damme, H., Murgaski, A., Qian, J., Ehling, M., Pretto, S., Bolli, E., Keirsse, J., Elkrim, Y., Martins, M. S., Fossoul, A., Lambrechts, D., Mazzone, M., Wullaert, A., Lamkanfi, M., Van Ginderachter, J. A., Laoui, D.
Abstract:
Interleukin-1{beta} (IL-1{beta}) 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-1{beta} in promoting cancer progression in patients, but the underlying mechanisms are little understood. Here, we show a key role for IL-1{beta} in driving tumor progression in two distinct mouse tumor models. Notably, inflammasome activation and GSDMD were dispensable for the production of intratumoral bioactive IL-1{beta}, which promoted systemic mobilization and infiltration of neutrophils into tumors. Neutrophils recruited via IL-1{beta} suppressed the acquisition of an effector T-cell phenotype and subsequent antitumor immune response. Moreover, IL-1{beta} was essential for neutrophil accumulation upon antiangiogenic therapy, thereby contributing to therapy-induced immunosuppression. Antitumor immunity in the absence of IL-1{beta}-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-1{beta} through establishing an immunosuppressive microenvironment and show that inflammasome activation is not essential for its release in tumors.
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Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2020.08.04.235796v1?rss=1
Authors: Kiss, M., Vande Walle, L., Lebegge, E., Van Damme, H., Murgaski, A., Qian, J., Ehling, M., Pretto, S., Bolli, E., Keirsse, J., Elkrim, Y., Martins, M. S., Fossoul, A., Lambrechts, D., Mazzone, M., Wullaert, A., Lamkanfi, M., Van Ginderachter, J. A., Laoui, D.
Abstract:
Interleukin-1{beta} (IL-1{beta}) 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-1{beta} in promoting cancer progression in patients, but the underlying mechanisms are little understood. Here, we show a key role for IL-1{beta} in driving tumor progression in two distinct mouse tumor models. Notably, inflammasome activation and GSDMD were dispensable for the production of intratumoral bioactive IL-1{beta}, which promoted systemic mobilization and infiltration of neutrophils into tumors. Neutrophils recruited via IL-1{beta} suppressed the acquisition of an effector T-cell phenotype and subsequent antitumor immune response. Moreover, IL-1{beta} was essential for neutrophil accumulation upon antiangiogenic therapy, thereby contributing to therapy-induced immunosuppression. Antitumor immunity in the absence of IL-1{beta}-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-1{beta} through establishing an immunosuppressive microenvironment and show that inflammasome activation is not essential for its release in tumors.
Copy rights belong to original authors. Visit the link for more info