Boveri Junior Research Group Innate Immunity

PD Dr. Adelheid Cerwenka

NK cells identified by brown staining infiltrating cervical carcinoma

The innate immune response serves as the first line of immune defense against cancer and does not only directly lead to tumor cell destruction, but also to efficient subsequent activation of the adaptive immune system. The Boveri Group “Innate Immunity” investigates Natural Killer (NK) cells in cancer, with the goal of improving therapeutic anti-tumor strategies. NK cells not only kill tumor cells, but can also produce inflammatory cytokines and activate cells of the adaptive immune system. Their activation is determined by a delicate balance between signals delivered by activating receptors and inhibitory receptors, most of which are specific for self-MHC class I. Many tumors lose expression of MHC class I molecules and escape from direct recognition by CD8+ T cells, but at the same time become highly susceptible to NK cell-mediated killing. In cancer patients, however, NK cell function is frequently severely impaired. To harness NK cells against tumors we are currently focused on i.) amplifying NK cell recognition of tumor cells by enhancing signals via activating receptors, ii.) identifying and exploiting checkpoints of NK cell activation in tumor beds, iii.) guiding high numbers of highly active NK cells into the tumor tissue, and iv.) generating long-lived NK cell populations with a sustained competence of effector function for NK cell adoptive transfer.

Our future projects will continue to develop strategies to harness NK cells against tumors. In particular, we will aim at identifying and targeting factors in the tumor microenvironment that counteract NK cell activation and cause NK cell exhaustion. In addition to NK cells, tissue resident NK related populations of innate lymphoid cells will be studied. These studies will potentially result in a novel class of NK cell checkpoint inhibitors. We will also explore the interaction of NK cells with adaptive cells during anti-tumor immune responses. Moreover, very recent evidence indicates that NK cells can remember previous exposure to antigens and cytokines, and the first evidence of NK cell memory formation in viral infection has been presented. Accordingly, in future projects we aim to exploit NK cell memory function for cancer therapy. Together, we will focus on gaining novel insight into mouse and human NK cell biology and the tumor microenvironment, building the basis for innovative strategies of immunotherapy against cancer.


PD Dr. Adelheid Cerwenka
Innate Immunity (D080)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 280
69120 Heidelberg
Tel: +49 6221 42 4480

Birgit Vey
Phone: +49 6221-42 3728

Selected Publications

  • 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.
  • Cerwenka A. et al. (2016). Natural killer cell memory in infection, inflammation and cancer. Nat Rev Immunol, 16(2), 112-123.
  • 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
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