Abstract 2685: Modulating tumor microenvironments through inflammasome and IL-1 pathways

Abstract

Abstract Chronic Inflammation has been shown to play important roles at all stages of tumor development including initiation, growth, invasion and metastasis. The inflammasome is an important innate immune pathway critical for the production of active IL-1β, a potent inflammatory cytokine. While extensive evidence indicates that inflammasomes are involved in infections and autoimmune diseases, the role of inflammasomes in tumor development remains controversial. To dissect the roles of the inflammasome and IL-1 pathway in tumor development, we utilized the MMTV-PyMT transgenic model, which develops mammary gland tumors with a high incidence of lung metastasis. Our results have demonstrated that inflammasome and IL-1β play a critical role in promoting tumor growth and metastasis. We found that tumor growth was associated with inflammasome activation and elevated levels of IL-1β in tumor microenvironments in mouse mammary tumor models and in human breast cancer tissues. Mice deficient for inflammasome components or IL-1R signaling exhibit significantly reduced lung metastasis. Our data also show that inflammasome activation led to the accumulation of myeloid cells, such as such as myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) in tumor microenvironments. Furthermore, blocking IL-1R signaling with IL-1R antagonist (IL-Ra) or anti-IL-1R antibody inhibited tumor growth and metastasis. Our results suggest that targeting the tumor microenvironment through inflammasome and IL-1 blockade may provide a novel approach for the treatment of breast cancer. Note: This abstract was not presented at the meeting. Citation Format: Beichu Guo, Jinyu Zhang, Shun-Jun Fu. Modulating tumor microenvironments through inflammasome and IL-1 pathways [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2685. doi:10.1158/1538-7445.AM2017-2685