Unexpected role of STAT1 serine727 for NK cell function

Natural killer (NK) cells are important key players of the innate immune system and provide immediate defense against viral infection and tumor transformation. Therefore, their potential in cancer immunotherapy has grown prominently in the last years [1]. As is known from the literature, the Signal Transducer and Activator of Transcription 1 (STAT1) plays an important role for NK cell function, since STAT1-deficient mice display impaired basal NK cytolytic activity in vitro and are unable to reject transplanted tumors in vivo [2]. STAT1 mediates signals downstream of interferons and gets activated by phosphorylation of several tyrosine and serine residues. In particular phosphorylation of S727 is considered a prerequisite for the full-fledged activation of STAT1 [3]. The aim of this project is to investigate the role of STAT1-S727 in NK cell-mediated cytotoxicity and tumor surveillance. Methods The analysis of STAT1−/−, STAT1-S727A and wild-type mice includes the preparation of primary splenic NK cells and their investigation regarding proliferation ([3H]thymidine-incorporation), cytotoxicity (standard [51Cr]-release) and cytokine production (ELISA