The M3 Research Center
Malignome, Metabolome and Microbiome

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574

Adresse: Otfried-Müller-Straße 37
72076 Tübingen

Office

Telefonnummer: +49 7071 29-82517
Dörte Brokering

E-Mail-Adresse: m3-office@med.uni-tuebingen.de

Experimental Immunology

Our lab investigates how the immune system functions in health and diseases such as cancer and viral infections, with a particular focus on understanding the spatial organization, cellular dynamics, and molecular determinants of immune responses in tumors and barrier tissues. We aim to decipher how immune cells act and cooperate within these complex environments, how their function is shaped by local tissue signals and the interaction with immune and non-immune cells, and how tumors exploit these mechanisms to evade immune attack. 

To achieve these aims, we integrate advanced immunological approaches, high-resolution imaging, single-cell and spatial transcriptomics and computational modelling into our work. We collaborate closely with an interdisciplinary network of researchers at the University of Tübingen and international partners, combining expertise from oncology, immunology, bioinformatics, and systems biology to drive biological discoveries and therapy invention. Our aim is that our work will help to identify new strategies and molecular targets for better cancer therapies and vaccines, and to identify new avenues to prevent and control immunopathologies. 

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Prof. Dr. rer. nat. Jan Böttcher

Prof. Dr. rer. nat. Jan Böttcher

Head of the research group

Personenprofil: Mehr zur Person

Jan Böttcher is a senior research group leader at the M3 Research Center and head of the Department of Experimental Immunology at the Institute of Immunology of the University of Tübingen. He is also Professor of Experimental Immunology at the Medical Faculty of the University of Tübingen.

Jan studied Molecular Biomedicine at the University of Bonn until 2008 and subsequently obtained a PhD in Immunology in 2013, focusing on anti-viral T cell immunity and memory development. He subsequently joined the CRUK London Research Institute and later the Francis Crick Institute in London, UK, for his postdoctoral research on cancer immunity, under the supervision of Caetano Reis e Sousa. In 2018, he returned to Germany and established his own lab at the Institute of Immunology at TU Munich, supported by an International Junior Research Group Grant from the Elite Network of Bavaria. He joined the University of Tübingen in 2025.
His research activities focus on understanding how immune responses are organized in tissues, identifying molecular mechanisms decisive for immunity to cancer and infection, and exploring ways of how to use this knowledge for immunotherapy invention. His contributions have been widely recognized and have been honored with multiple awards, including the Georges-Köhler Prize from the German Society of Immunology (2024), the Fleur Hiege-Gedächtnispreis (2024) and the Fritz-und-Ursula-Melchers Prize (2018) from the German Society of Immunology.


  • Department of Experimental Immunology, Institute of Immunology, University of Tübingen
  • Institute of Molecular Immunology, TUM University Hospital, Technical University of Munich (TUM), Munich, Germany
Gruppenfoto vor dem Gebäude
Bastian Kruse

Bastian Kruse

Postdoctoral Researcher

Personenprofil: Mehr zur Person

Maria Galvez de Villalta

Maria Galvez de Villalta

Executive Assistant | Administrative Coordinator

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Herr Boris Dymov

Herr Boris Dymov

PhD student

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Anna-Marie Pedde

Anna-Marie Pedde

Postdoctoral Researcher

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Herr Lukas Ramsauer

Herr Lukas Ramsauer

PhD Student

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Anna Hirschberger

Anna Hirschberger

Student Assistant

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Herr Dmytro Hlushchenko

Herr Dmytro Hlushchenko

PhD Student

Personenprofil: Mehr zur Person

Immunity
in cancer and infection
Molecular mechanisms
determining immune cell function
Spatial organization
and dynamics of immune networks in tissues

Selected publications

  • 2026

    Ablation of PGE2-signaling through dual receptor knock-out in CAR T cells enhances therapeutic efficacy in solid tumors

    Dörr J.*, Gregor L.*, Lacher S.B.*, Oner A., Sun Y., Piseddu I., Fertig L., Spajic S., Lesch S., Michaelides S., Seifert M., Gottschlich A., Majed L., Briukhovetska D., Simnica D., Hartmann V., Grosshauser K., Andreu-Sanz D., Carlini E., Stock S., Holtermann A., Müller P.J., Strzalkowski T., Trefny M., Endres S., Jenkins R.W., Böttcher J.P.$, Kobold S.$ (2026). Ablation of PGE2-signaling through dual receptor knock-out in CAR T cells enhances therapeutic efficacy in solid tumors. Nat. Biomed. Eng. In press.
  • 2025

    Prostaglandins in cancer revisited: principles of production, mechanisms of immune regulation, and therapeutic perspectives

    Müller E.*, Kruse B.*, Böttcher J.P. (2025). Prostaglandins in cancer revisited: principles of production, mechanisms of immune regulation, and therapeutic perspectives.
    Blood. blood.2025029806. https://doi.org/10.1182/blood.2025029806
  • 2025

    Two-layered immune escape in AML is overcome by Fcγ receptor activation and inhibition of PGE2 signaling in NK cells

    Rothfuß C., Baumann T.,  Donakonda S., Brauchle B., Marcinek A., Urban C., Mergner J., Pedde A.-M., Hirschberger A., Krupka C., Neumann A.-S., Hänel G., Merten C., Öllinger R., Hecker J.S., Bauer T., Schmid C., Götze K.S., Altomonte J., Bücklein V., Jacobs R.,  Rad R.,  Dawid C.,  Simeoni L., Schraven B.,  Pichlmair A.,  Subklewe M.,  Knolle P.A.,  Böttcher J.P.,  Höchst B. (2025). Two-layered immune escape in AML is overcome by Fcγ receptor activation and inhibition of PGE2 signaling in NK cells.
    Blood.145 (13): 1395–1406. https://doi.org/10.1182/blood.2024025706
  • 2024

    Cancer cells impair monocyte-mediated T cell stimulation to evade immunity

    Elewaut, A., Estivill G., Bayerl F., Castillon L., Novatchkova M., Pottendorfer E., Hoffmann-Haas L., Schönlein M., Nguyen T.V., Lauss M., Andreatta F., Vulin M., Krecioch I., Bayerl J., Pedde A.-M., Fabre N., Holstein F., Cronin S.M., Rieser S., Laniti D.D., Barras D., Coukos G., Quek C., Bai X., i Ordoño M.M., Wiesner T., Zuber J., Jönsson G., Böttcher J.P., Vanharanta S., Obenauf A.C.. (2025). Cancer cells impair monocyte-mediated T cell stimulation to evade immunity. Nature. 637: 716-725. https://doi.org/10.1038/s41586-024-08257-4
  • 2024

    Tissue-colonizing disseminated tumor cells secrete prostaglandin E2 to promote NK cell dysfunction and evade anti-metastatic immunity

    Pedde, A.-M., Kim H., Donakonda S., Baumann T., Bayerl F., Meiser P., Hirschberger A., Klement C., Grassmann S., Öllinger R., Hüser N., Hartmann D., Laschinger M., Trapani J. A., Zippelius A., Bald T., Wiedemann G.M., Rad R., Sun J.C., Höchst B., Böttcher J.P. (2024). Tissue-colonizing disseminated tumor cells secrete prostaglandin E2 to promote NK cell dysfunction and evade anti-metastatic immunity.
    Cell Reports. 43: 114855. https://doi.org/10.1016/j.celrep.2024.114855
  • 2024

    A PKA-operated liver tissue-rheostat curbs TCR signalling and effector function of virus-specific CD8 T cells in chronic hepatitis B virus infection

    Bosch M., Kallin N., Donakonda S., Zhang J.D., Wintersteller H., Hegenbarth S., Heim K., Ramirez, C., Fürst A., Lattouf E.I., Feuerherd M., Chattopadhyay S., Kumpesa N., Griesser V., Hoflack J.C., Siebourg-Polster J., Mogler C., Swadling L., Pallett L.J., Meiser P., Manske K., de Almeida, G.P., Kosinska A.D., Sandu I., Schneider S., Steinbacher V., Teng Y., Schnabel J., Theis F., Gehring A.J., Boonstra A., Janssen H., Vandenbosch M., Cuypers E., Öllinger R., ENgleitner T. Rad R., Steiger K., Oxenius A., Lo Wa.L., Klepsch V., Bayer G., Holzmann B., Maini M.K., Heeren R., Murray P.J., Thimme R., Herrmann C., Protzer U., Böttcher J.P., Zehn D., Wohlleber D., Mauer G.M., Hofmann M., Luangsay S., Knolle P.A. (2024).  A PKA-operated liver tissue-rheostat curbs TCR signalling and effector function of virus-specific CD8 T cells in chronic hepatitis B virus infection.
    Nature. 631, 867–875. https://doi.org/10.1038/s41586-024-07630-7
  • 2024

    PGE2 limits effector expansion of tumour-infiltrating stem-like CD8+ T cells

    Lacher S., Dörr J., de Almeida G.P., Hönninger J., Meiser P., Bayerl F., Hirschberger A., Pedde A.M., Meiser P., Ramsauer L., Rudolph T.J., Spranger N., Morotti M., Jarosch S., Gregors L., Oner A., Gregor L., Lesch S., Michaelides S., Fertig L., Briukhovetska D., Majed L., Stock S., Busch D.H., Buchholz V.R., Knolle P.A., Zehn D., Kobold S.$, Böttcher J.P.$ (2024). PGE2 limits effector expansion of tumour-infiltrating stem-like CD8+ T cells. Nature. 629, 417–425.  https://doi.org/10.1038/s41586-024-07254-x
  • 2024

    PGE2 inhibits TIL expansion by disrupting IL-2 signalling and metabolism

    Morotti M., Grimm A.J., Hope H., Arnaud M., Desbuisson M., Rayroux N., Barras D., Masid M., Murgues B., Chap B., Ongaro M., Rota I., Ronet C., Minasyan A., Ouchen K., Mjahed R-B., Benedetti F., Abdellaoui N., Turrini R., Gannon P., Zaman P., Mathevet P., Lelievre L., Crespo I., Conrad M., Verdeil G., Kandalaft L., Dagher J., Corria-Osorio J., Doucey M-A., Ho P-C., Harari A., Vannini N., Böttcher J.P., Dangaj Laniti D., Coukos G (2024). PGE2 inhibits TIL expansion by disrupting IL-2 signalling and metabolism. Nature. 629, 426–434.  https://doi.org/10.1038/s41586-024-07352-w
  • 2023

    A distinct stimulatory cDC1 subpopulation amplifies CD8+ T cell responses in tumors for protective anti-cancer immunity

    Meiser P., Knolle M., Hirschberger A., Gustavo P.A., Lacher S., Bayerl F., Pedde A.M., Flommersfeld S., Hönninger J., Stark L., Stögbauer F., Anton M., Wirth M., Wohlleber D., Steiger K., Buchholz V.R., Wollenberg B., Zielinski C.E., Braren R., Rückert D., Knolle P.A., Kaissis G.*, Böttcher J.P.$ (2023). A distinct stimulatory cDC1 subpopulation amplifies CD8+ T cell responses in tumors for protective anti-cancer immunity. Cancer Cell. 41(8):1498-1515.e10.   https://doi.org/10.1016/j.ccell.2023.06.008
  • 2023

    Tumor-derived PGE2 programs cDC1 dysfunction to impair intratumoral orchestration of anti-cancer T cell responses

    Bayerl F., Meiser P., Donakonda S., Hirschberger A., Lacher S., Pedde A.M., Hermann C.D., Knolle M., Rudolph T.J., Grassmann S., Öllinger R., Kirchhammer N., Trefny M., Elewaut A., Anton M., Wohlleber D., Höchst B., Zaremba A., Krüger A., Rad R., Obenauf A.C., Schadendorf D., Zippelius A., Buchholz V.R., Schraml B.U., Böttcher J.P. (2023). Tumor-derived PGE2 programs cDC1 dysfunction to impair intratumoral orchestration of anti-cancer T cell responses. Immunity. 1341-2458. e11.   https://doi.org/10.1016/j.immuni.2023.05.011
  • 2023

    Guidelines for visualization and analysis of DC in tissues using multiparameter fluorescence microscopy imaging methods

    Bayerl F., Bejarano D.A., Bertacchi G., Doffin A.-C., Gobbini E., Hubert M., Li L., Meiser P., Müller L., Pedde A.-M., Posch W., Schlitzer A., Schmitz M., Schraml B., Uderhardt S., Valladeau-Guilemond J., Wilflingseder D., Zaderer V., Böttcher J.P. (2023). Guidelines for visualization and analysis of DC in tissues using multiparameter fluorescence microscopy imaging methods. Eur. J. Immunol. 2249923 https://doi.org/10.1002/eji.202249923
  • 2021

    Auto-aggressive CXCR6+ CD8 T cells cause liver immune pathology in NASH

    Dudek M., Pfister D., Donakonda S., Filpe P., Schneider A., Laschinger M., Hartmann D., Hüser N., Meiser P., Bayerl F., Inverso D., Wigger J., Sebode M., Öllinger R., Rad R., Hegenbarth S., Anton M., Guillot A., Bowman A., Heide D., Müller F., Ramadori P., Leone V., Garcia-Caceres C., Gruber T., Seifert G., Kabat A.M., Mallm J.-P., Reider S., Effenberger M., Roth S., Billeter A.T., Müller-Stich B., Pearce E.J.,  Koch-Nolte F., Käser R., Tilg H., Thimme R., Boettler T., Tacke F., Dufour J.F., Haller D., Murray P., Heeren R., Zehn D., Böttcher J.P., Heikenwälder M., Knolle P.A. (2021). Auto-aggressive CXCR6+ CD8 T cells cause liver immune pathology in NASH.
    Nature. 592: 444-449. https://doi.org/10.1038/s41586-021-03233-8
  • 2021

    Fate mapping of single NK cells identifies a type 1 innate lymphoid-like lineage that bridges innate and adaptive recognition of viral infection

    Flommersfeld S., Böttcher J.P., Ersching J., Flossdorf M., Meiser P., Pachmayr L.O., Leube J., Hensel I., Jarosch S., Zhang Q., Chaudhry M.Z., Andrae I., Schiemann M., Busch D.H., Cicin-Sain L., Sun J.C., Gasteiger G., Victora G.D., Höfer T., Buchholz V.R. and Grassmann S. (2021). Fate mapping of single NK cells identifies a type 1 innate lymphoid-like lineage that bridges innate and adaptive recognition of viral infection. Immunity. 54: 2288-2304.e7. https://doi.org/10.1016/j.immuni.2021.08.002
  • 2018

    The role of type 1 conventional dendritic cells in cancer immunity

    Böttcher, J.P.† and Reis e Sousa, C.† (2018). The role of type 1 conventional dendritic cells in cancer immunity.
    Trends in Cancer. 4: 784–792. https://doi.org/10.1016/j.trecan.2018.09.001
  • 2018

    NK Cells Stimulate Recruitment of cDC1 into the Tumor Microenvironment Promoting Cancer

    Böttcher, J.P., Bonavita, E., Chakravarty, P., Blees, H., Cabeza-Cabrerizo, M., Sammicheli, S., Rogers, N.C., Sahai, E., Zelenay, S., Reise Sousa, C†. (2018). NK Cells Stimulate Recruitment of cDC1 into the Tumor Microenvironment Promoting Cancer. Immune Control. Cell 172: 1022–1037. https://doi.org/10.1016/j.cell.2018.01.004