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Natural Killer Cells in Inflammation and Cancer

The innate immune response serves as initiator and modulator of the immune defense against invading pathogens and tumors. The overall goals of our research are 1.) to dissect and empower activation modules of Natural Killer (NK) cells and tissue-resident Innate Lymphoid Cells (ILC) and 2.) to understand the influence of the tissue microenvironment on their function during homeostasis and disease.

To decipher the role of NK and ILCs we not only use mouse models of colon/liver/skin cancer and inflammation, but also develop sophisticated co-culture models mimicking hepatitis infection and human cancer microenvironments. It is our ultimate goal to improve the current immunotherapy of inflammatory and malignant disease by exploiting the innate immune system. 

Key Publications

  1. von Kries A, Garcés-Lázaro I, Balzasch B, Sticht C, Shaltiel IA, Boonekamp KE, Sams A, Burgermeister E, Betge J, Ebert M, Boutros M, Helming L, Stojanovic A, Cerwenka A. Colorectal cancer organoids drive hypoxia, TGF-β, and patient-specific diversification of NK cell activation programs, 2025, J Immunother. Cancer. JITC, 2025 Dec 5;13(12):e012988. doi: 10.1136/jitc-2025-012988.PMID: 41360426
  2. Kilian M, Friedrich MJ, Lu KH, Vonhören D, Jansky S, Michel J, Keib A, Stange S, Hackert N, Kehl N, Hahn M, Habel A, Jung S, Jähne K, Sahm F, Betge J, Cerwenka A, Westermann F, Dreger P, Raab MS, Meindl-Beinker NM, Ebert M, Bunse L, Müller-Tidow C, Schmitt M, Platten M. The immunoglobulin superfamily ligand B7H6 subjects T cell responses to NK cell surveillance. Sci Immunol. 2024 May 3;9(95):eadj7970. doi: 10.1126/sciimmunol.adj7970.
  3. Hofman T, Siu Wang Ng, Garcés-Lázaro I, Heigwer F, Boutros M, Cerwenka A. IFNγ mediates the resistance of tumor cells to distinct NK cell subsets. Journal of Immunother. Cancer, JITC (2024) DOI: 10.1136/jitc-2024-009410
  4. Papaioannou S, See J-X, Jeong M, De La Torre C, Reiners-Koch P-S, Sati A, Mogler C, Platten M, Cerwenka A*, Stojanovic A*. Liver sinusoidal endothelial cells orchestrate NK cell recruitment and activation in acute inflammatory liver injury. Cell Rep. (2023) 42(8):112836. DOI: 10.1016/j.celrep.2023.112836. *shared last authors
  5. Ni J, Wang X, Stojanovic A, Zhang Q, Wincher M, Bühler L, Arnold A, Correia MP, Winkler M, Koch PS, Sexl V, Höfer T, Cerwenka A. Single-Cell RNA Sequencing of Tumor-Infiltrating NK Cells Reveals that Inhibition of Transcription Factor HIF-1α Unleashes NK Cell Activity. Immunity (2020) 52,1075-1087.e8. DOI: 10.1016/j.immuni.2020.05.001 (open access)
  6. Correia MP, Stojanovic A, Bauer K, Juraeva D, Tykocinski LO, Lorenz HM, Brors B, Cerwenka A. Distinct human circulating NKp30+FcεRIγ+CD8+ T cell population exhibiting high natural killer-like antitumor potential. PNAS (2018) 115, E5980-E5989. DOI: 10.1073/pnas.1720564115 (open access)
  7. Pahl JHW, Koch J, Gotz JJ, Arnold A, Reusch U, Gantke T, Rajkovic E, Treder MS, Cerwenka A. CD16A activation of NK cells promotes NK cell proliferation and memory-like cytotoxicity against cancer cells. Cancer Immunol. Res. (2018) 6, 517-527. DOI: 10.1158/2326-6066.CIR-17-0550 (open access)
  8. Pollmann J, Götz JJ, Rupp D, Strauss O, Granzin M, Grünvogel O, Mutz P, Kramer C, Lasitschka F, Lohmann V, Björkström NK, Thimme R, Bartenschlager R, Cerwenka A. Hepatitis C virus-induced natural killer cell proliferation involves monocyte-derived cells and the OX40/OX40L axis. J. Hepatol. (2018) 68, 421-430. DOI: 10.1016/j.jhep.2017.10.021
  9. Cerwenka A, Lanier LL. NK cell memory in viral infection, inflammation and cancer. Nat. Rev. Immunol. (2016) 16, 112-23. DOI: 10.1038/nri.2015.9 (open access)
  10. Cerwenka A, Bakker ABH, McClanahan T, Wagner J, Wu J, Phillips JH and Lanier LL. Retinoic acid early inducible genes define a ligand family for the activating NKG2D receptor in mice. Immunity (2000) 12, 721-727. DOI: 10.1016/s1074-7613(00)80222-8 (open access)
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