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IL-15 is an inflammatory mediator in the tumor microenvironment
  1. Scott M Anthony1,
  2. Gabriel Pham2 and
  3. Kimberly S Schluns3
  1. Aff1 grid.240145.60000000122914776University of Texas MD Anderson Cancer Center/Department of Immunology/The University of Texas Graduate School of Biomedical Sciences at Houston Houston TX USA
  2. Aff2 grid.24827.3b0000000121799593University of Cincinnati College of Medicine Cincinnati OH USA
  3. Aff3 grid.240145.60000000122914776The University of Texas MD Anderson Cancer Center/Department of Immunology Houston TX USA

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Meeting abstracts

Previous studies have shown that activation of the Stimulator of Interferon Genes (STING) pathway is important for regulating type I Interferons (IFN) in tumors. Furthermore, tumor DNA induces IL-15 and IL-15Rα mRNA in cultured dendritic cells (DC) in a STING-dependent manner. Since we have recently shown type I IFNs induce soluble IL-15Rα/IL-15 complexes (sIL-15 complexes), we set out to determine if sIL-15 complexes are produced in tumor microenvironment and are regulated by STING signaling. To determine if STING induces sIL-15 complexes, mice were given STING agonists (c-di-GMP) either i.v. or i.p. One day later, sIL-15 complexes were increased in serum and splenic homogenates of STING-treated mice. In addition, STING agonists directly induced sIL-15 complexes in BM-derived DCs. To examine sIL-15 complexes in the tumor microenvironment, B16-F10 tumors of various sizes were isolated from mice and sIL-15 complexes were measured in homogenates from tumors, draining lymph nodes, and spleen. Interestingly, levels of sIL-15 complexes were high in homogenates from small tumors (less than 100mm2) and their draining lymph nodes but low in larger tumors. These findings suggest IL-15 is an inflammatory factor produced during early tumor development. To investigate the role of IL-15 within the tumor microenvironment, we analyzed tumor growth in mice conditionally deleted of IL-15Rα (IL-15Rα floxed X ER-Cre Tg). Unlike IL-15Rα-/- mice, this model system allows examination of lymphocytes that have developed in the presence of IL-15 signals. In mice conditionally deleted of IL-15Rα (Tamoxifen-treated IL-15Rα floxed X ER-Cre Tg mice), tumor growth was increased compared to control mice (Tamoxifen treated IL-15Rα floxed mice). Overall, these studies suggest that IL-15 is a component of the inflammatory milieu of the tumor microenvironment that likely contributes to native anti-tumor responses. This work was supported by a seed fund from the Center for Inflammation and Cancer at the MD Anderson Cancer Center and a Cancer Prevention and Research Institute of Texas Research Training Award.