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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

Ferreira C, Barros L, Baptista M, Blankenhaus B, Barros A, Figueiredo-Campos P, Konjar Š, Lainé A, Kamenjarin N, Stojanovic A, Cerwenka A, Probst HC, Marie JC, Veldhoen M. Type 1 Treg cells promote the generation of CD8+ tissue-resident memory T cells. Nat Immunol. 2020 Jul;21(7):766-776. doi: 10.1038/s41590-020-0674-9. Epub 2020 May 18.

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 Jun 16;52(6):1075-1087.e8. doi: 10.1016/j.immuni.2020.05.001. Epub 2020 May 22.PMID: 32445619

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. Proc Natl Acad Sci U S A. 2018 Jun 12. pii: 201720564. doi: 10.1073/pnas.1720564115. [Epub ahead of print]

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 Mar;68(3):421-430. doi: 10.1016/j.jhep.2017.10.021. Epub 2017 Nov 1.

Cerwenka A, Lanier LL, 2016, NK cell memory in viral infection, inflammation and cancer, Nature Immunology Reviews; Feb;16(2):112-23. doi: 10.1038/nri.2015.9.

Rölle A, Pollmann J, Ewen E, Halenius A, Hengel H, Cerwenka A. 2014. IL-12 producing monocytes and HLA-E drive NKG2C+ NK cell expansion in HCMV infection, J. Clin. Invest. Nov 10. pii: 77440. doi: 10.1172/JCI77440.

Ni J, Miller M, Stojanovic A, Garbi N, Cerwenka A. 2012, Sustained effector function of IL-12/15/18 preactivated NK cells against established tumors. J Exp Med 209(13):2351-2365.