Boveri Junior Research Group Innate Immunity
PD Dr. Adelheid Cerwenka
The innate immune response serves as the first line of immune defence and does not only directly lead to tumor cell destruction, but also to efficient subsequent activation of the adaptive immune system. The Boveri Junior Group „Innate Immunity“ investigates Natural Killer (NK) cells and myeloid cell subsets in cancer with the goal to improve therapeutic anti-tumor strategies. NK cells potently kill tumor cells and produce inflammatory cytokines. Their activation is determined by a delicate balance between signals delivered by inhibitory receptors, most of which are specific for self-MHC class I, and activating receptors. Many tumors lose expression of MHC class I molecules and frequently escape from direct recognition by CD8+ T cells, but become highly susceptible to NK cell-mediated killing. Thus, we believe that it is of major importance to explore NK cell-based therapies against cancer. Our research focuses on three strategies to amplify innate immune cell-mediated anti-tumor responses. 1.) It is our goal to guide high numbers of highly active, persistent NK cells to the tumor site. 2.) We attempt to increase the visibility of tumor cells to NK cells by the upregulation of ligands for activating NK cell receptors on tumors. 3.) We aim at exploring inflammatory pathways in myeloid cells and their functional importance in the context of cancer.Our future projects will further continue to develop strategies aiming at harnessing NK cells against tumors. In addition, candidates in inflammatory signalling pathways in myeloid cells and their functional importance in the context of cancer inflammation will be investigated. Our overall program is designed to gain novel insight in mouse and human NK cell and myeloid cell biology building the basis for innovative strategies of immunotherapy against cancer.
Fiegler N, Textor S, Arnold A, Rölle A, Oehme I, Breuhahn K, Moldenhauer G, Witzens-Harig M, Cerwenka A. Downregulation of the activating NKp30 ligand B7-H6 by HDAC inhibitors impairs tumor cell recognition by NK cells. Blood. 2013 Jun 25. [Epub ahead of print] PMID: 23801635
Rölle A, Pollmann J, Ewen EM, Le VT, Halenius A, Hengel H, Cerwenka A. IL-12-producing monocytes and HLA-E control HCMV-driven NKG2C+ NK cell expansion. J Clin Invest. 2014 Dec;124(12):5305-16. doi: 10.1172/JCI77440. Epub 2014 Nov 10.
Schlecker E, Stojanovic A, Eisen C, Quack C, Falk CS, Umansky V and Cerwenka A. Tumor-infiltrating monocytic myeloid-derived suppressor cells mediate CCR5-dependent recruitment of regulatory T cells favoring tumor growth” J Immunol. 189(12):5602-5611, 2012
Ni J, Miller M, Stojanovic A, Garbi N, Cerwenka A. Sustained effector function of IL-12/15/18 preactivated NK cells against established tumors. J Exp Med 209(13):2351-2365, 2012