Abstract 520: Regulation of natural killer cell development and antitumor immunity by the IL-15 system

Natural killer (NK) cells are innate immune cells involved in tumor surveillance. The development and effector function of NK cells require IL-15 signal, which is “trans-presented” to IL-15Rβγ on NK cells by IL-15Rα on neighboring cells. Because the IL-15Rα intracellular (IC) domain has the capacity to recruit signaling molecules, we generated knock-in (KI) and transgenic (Tg) mice that lack the IC domain to assess independently the role of the IL-15 trans-presentation level. In this study, we found that the IL-15Rα level on bone marrow-derived dendritic cells (BMDCs) generated by KI and Tg mice determines the level of Stat5 phosphorylation in NK cells, thus offering the opportunity to study quantitative effects of IL-15 trans-presentation on NK cell development and function in vivo. We also found that NK cell homeostasis, mature NK cell differentiation, and acquisition of effector functions require different levels of IL-15 trans-presentation input to achieve full status. In order to investigate the effects of IL-15 trans-presentation level in anti-tumor immunity in vivo, we established the tumor inoculation experiment. Our preliminary data showed that the growth of B16/OVA melanoma increased in Il15−/− mice in comparison to WT mice. We will assess the role of the IL-15 system in anti-tumor immunity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 520. doi:1538-7445.AM2012-520