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.
Experimental Immunology
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.
Biosketch
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.
Interview
Experimental Immunology – Interview with Prof. Dr. rer. nat. Jan Böttcher
In this interview, Prof. Dr. rer. nat. Jan Böttcher talks about his research in experimental immunology, where his team combines mathematical modeling, bioinformatics, and advanced microscopy techniques to better understand how the immune system responds to cancer. He explains that their work focuses on identifying molecular mechanisms and immune checkpoints that could improve tumor control and lead to more effective immunotherapies. The overall goal is to translate these discoveries into new treatment strategies for cancer and chronic diseases.
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Co-Affiliations
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Department of Experimental Immunology, Institute of Immunology, University of Tübingen
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Institute of Molecular Immunology, TUM University Hospital, Technical University of Munich (TUM), Munich, Germany
Team
Executive Assistant | Administrative Coordinator
Immunity
in cancer and infection
Molecular mechanisms
determining immune cell function
Spatial organization
and dynamics of immune networks in tissues
Selected publications
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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 SB*, Oner A, Sun Y, Piseddu I, Fertig L, Spajic S, Lesch S, Michaelides S, Seifert M, Gottschlich A, Samson N, Majed L, Briukhovetska D, Simnica D, Hartmann V, Gabriel K, Cohen S, Boland GM, Andreu-Sanz D, Carlini E, Stock S, Holtermann A, Müller PJ, Strzalkowski T, Trefny MP, Endres S, Jenkins RW, Böttcher JP, Kobold S. Ablation of prostaglandin E2 signalling through dual receptor knockout in CAR T cells enhances therapeutic efficacy in solid tumours.
Nat Biomed Eng. 2026 Apr;10(4):697-710. doi: 10.1038/s41551-025-01610-6. Epub 2026 Feb 11. PMID: 41673138; PMCID: PMC13099425.
https://doi.org/10.1038/s41551-025-01610-6 -
2026
Prostaglandins in cancer revisited: principles of production, mechanisms of immune regulation, and therapeutic perspectives
Müller E*, Kruse B*, Böttcher JP. Prostaglandins in cancer revisited: principles of production, mechanisms of immune regulation, and therapeutic perspectives.
Blood. 2026 Feb 12;147(7):713-724.
https://doi.org/10.1182/blood.2025029806 -
2026
Positioning and reversible suppression of CCR7+ dendritic cells in perivascular tumor niches shape cancer immunity
Zitti B*, Duval F*, Wirapati P, Hicham M, Xie Y, Oh J, Hoelzl J, Meiser P, Varrone M, Peterson HM, Cianciaruso C, Bill R, Bayerl F, Bolli E, Goubet AG, Kiss M, McDowell S, Cheng P, Celestini D, Terzic J, Zwahlen T, Alouche N, Zouggari N, Tarussio D, Tissot S, Nunes-Hasler P, Mino-Kenudson M, Lanuti M, Faquin WC, Sadow PM, Tille JC, Intidhar Labidi-Galy S, Garris CS, Hugues S, Petrova TV, Ludewig B, Quezada S, Luther S, Mempel TR, Ciriello G, Pai SI, Michielin O, Böttcher JP, Weissleder R, Pittet MJ. Positioning and reversible suppression of CCR7+ dendritic cells in perivascular tumor niches shape cancer immunity.
Immunity. 2026 Jan 13;59(1):161-176.e12. doi: 10.1016/j.immuni.2025.11.020. Epub 2025 Dec 19. PMID: 41421339; PMCID: PMC12882814.
https://doi.org/10.1016/j.immuni.2025.11.020 -
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