Focus
One major goal of our group is to explore the interaction between different cellular components of the immune system with tumor cells and to develop strategies to manipulate the immune system for a more efficient treatment of malignant diseases. In this context, we investigate the characteristics of tumor-infiltrating dendritic cells (DCs) and theirimpact on the prognosis of patients. We also explore the modulation of important immunostimulatory properties of human DCs by tumor cells. In addition, we focus on the identification of novel tumor-associated antigens for T cell- and antibody-based immunotherapy of tumor patients.
Selected publications
Peuker K, Strigli A, Tauriello DVF, Hendricks A, von Schönfels W, Burmeister G, Brosch M, Herrmann A, Krüger S, Nitsche J, Južnić L, Geissler MM, Hiergeist A, Gessner A, Wirbel J, Priyadarshini Ponnudurai R, Voogdt CGP, Tunger A, Wehner R, Stange DE, Weitz J, Aust DE, Baretton GB, Schmitz M, Röcken C, Hampe J, Hinz S, Zeller G, Chavakis T, Schafmayer C, Batlle E, Zeissig. Microbiota-dependent activation of the myeloid calcineurin-NFAT pathway inhibits B7H3- and B7H4-dependent anti-tumor immunity in colorectal cancer. Immunity. 2022;55:701-717.
Tirado-Gonzalez I, Descot A, Soetopo D, Nevmerzhitskaya A, Schäffer A, Kur IM, Czlonka E, Wachtel C, Tsoukala I, Müller L, Schäfer AL, Weitmann M, Dinse P, Alberto E, Buck MC, Landry JJM, Baying B, Slotta-Huspenina J, Roesler J, Harter PN, Kubasch AS, Meinel J, Elwakeel E, Strack E, Tran Quang C, Abdel-Wahab O, Schmitz M, Weigert A, Schmid T, Platzbecker U, Benes V, Ghysdael J, Bonig H, Götze KS, Rothlin CV, Ghosh S, Medhouf H. AXL inhibition in macrophages stimulates host-versus-leukemia immunity and eradicates naïve and treatment resistant leukemia. Cancer Discov. 2021;11:2924-2943.
Kießler M, Plesca I, Sommer U, Wehner R, Wilczkowski F, Müller L, Tunger A, Lai X, Rentsch A, Peuker K, Zeissig S, Seifert AM, Seifert L, Weitz J, Bachmann M, Bornhäuser M, Aust D, Baretton G, Schmitz M. Tumor-infiltrating plasmacytoid dendritic cells are associated with survival in human colon cancer. J Immunother Cancer. 2021;9:e001813.
Vadakekolathu J, Minden MD, Hood T, Church SE, Reeder S, Altmann H, Sullivan AH, Viboch EJ, Patel T, Ibrahimova N, Warren SE, Arruda A, Liang Y, Smith TH, Foulds GA, Bailey MD, Gowen-MacDonald J, Muth J, Schmitz M, Cesano A, Pockley AG, Valk PJM, Löwenberg B, Bornhäuser M, Tasian SK, Rettig MP, Davidson-Moncada JK, DiPersio JF, Rutella S. Immune landscapes predict chemotherapy resistance and immunotherapy response in acute myeloid leukemia. Sci Transl Med. 2020;12:eaaz0463.
Plesca I, Tunger A, Müller L, Wehner R, Lai X, Grimm MO, Rutella S, Bachmann M, Schmitz M. Characteristics of tumor-infiltrating lymphocytes prior to and during immune checkpoint inhibitor therapy. Front Immunol. 2020;11:364.
Rammensee HG, Wiesmüller KH, Chandran PA, Zelba H, Rusch E, Gouttefangeas C, Kowalewski DJ, Di Marco M, Haen SP, Walz JS, Gloria YC, Bödder J, Schertel JM, Tunger A, Müller L, Kießler M, Wehner R, Schmitz M, Jakobi M, Schneiderhan-Marra N, Klein R, Laske K, Artzner K, Backert L, Schuster H, Schwenck J, Weber ANR, Pichler BJ, Kneilling M, la Fougère C, Forchhammer S, Metzler G, Bauer J, Weide B, Schippert W, Stevanović S, Löffler MW. A new synthetic toll-like receptor 1/2 ligand is an efficient adjuvant for peptide vaccination in a human volunteer. J Immunother Cancer. 2019;7:307.
Heidenreich F, Rücker-Braun E, Walz JS, Eugster A, Kühn D, Dietz S, Nelde A, Tunger A, Wehner R, Link CS, Middeke JM, Stölzel F, Tonn T, Stevanovic S, Rammensee HG, Bonifacio E, Bachmann M, Zeis M, Ehninger G, Bornhäuser M, Schetelig J, Schmitz M. Mass spectrometry-based identification of a naturally presented receptor tyrosine kinase-like orphan receptor 1-derived epitope recognized by CD8+ cytotoxic T cells. Haematologica. 2017;102:e460-e464.
Toma M, Wehner R, Kloß A, Hübner L, Fodelianaki G, Erdmann K, Füssel S, Zastrow S, Meinhardt M, Seliger B, Brech D, Noessner E, Tonn T, Schäkel K, Bornhäuser M, Bachmann MP, Wirth MP, Baretton G, Schmitz M. Accumulation of tolerogenic human 6-sulfo LacNAc dendritic cells in renal cell carcinoma is associated with poor prognosis. Oncoimmunology. 2015;4:e1008342.
Cosgun KN, Rahmig S, Mende N, Reinke S, Hauber I, Schäfer C, Petzold A, Weisbach H, Heidkamp G, Purbojo A, Cesnjevar R, Platz A, Bornhäuser M, Schmitz M, Dudziak D, Hauber J, Kirberg J, Waskow C. Kit regulates HSC engraftment across the human-mouse species barrier. Cell Stem Cell. 2014;15:227-38.
Döbel T, Kunze A, Babatz J, Tränkner K, Ludwig A, Schmitz M, Enk A, Schäkel K. FcyRIII equips immature 6-sulfo LacNAc-expressing dendritic cells (slanDCs) with a unique capacity to handle IgG-complexed antigens. Blood. 2013;123:3609-18.
Bornhäuser M, Thiede C, Platzbecker U, Kiani A, Oelschlaegel U, Babatz J, Lehmann D, Hölig K, Radke J, Tuve S, Wermke M, Wehner R, Jähnisch H, Bachmann MP, Rieber EP, Schetelig J, Ehninger G, Schmitz M. Prophylactic transfer of BCR-ABL-, PR1-, and WT1-reactive donor T cells after T-cell-depleted allogeneic hematopoietic cell transplantation in patients with chronic myeloid leukemia. Blood. 2011;117:7174-84.
Hänsel A, Günther C, Ingwersen J, Starke J, Schmitz M, Bachmann M, Meurer M, Rieber EP, Schäkel K. Human slan (6-sulfo LacNAc) dendritic cells are inflammatory dermal dendritic cells in psoriasis and drive strong Th17/Th1 T-cell responses. J Allergy Clin Immunol. 2011;127:787-94.
Wehner R, Schumacher P, Bornhäuser M, Ehninger G, Schäkel K, Bachmann M, Schmitz M. Acute myeloid leukemia cells fail to activate human dendritic cells: a potential mechanism of immune evasion. Leukemia. 2010:24:1965-7.
Kiessling A, Füssel S, Wehner R, Bachmann M, Wirth MP, Rieber EP, Schmitz M. Advances in specific immunotherapy for prostate cancer. Eur Urol. 2008;53:694-708.
Straube C, Wehner R, Wendisch M, Bornhäuser M, Bachmann M, Rieber EP, Schmitz M. Bortezomib significantly impairs the immunostimulatory capacity of human myeloid blood dendritic cells. Leukemia. 2007;21:1464-71.
Schmitz M, Zhao S, Schäkel K, Bornhäuser M, Ockert D, Rieber EP. Native human blood dendritic cells as potent effectors in antibody-dependent cellular cytotoxicity. Blood. 2002;100:1502-4.
Schmitz M, Diestelkoetter P, Weigle B, Schmachtenberg F, Stevanovic S, Ockert D, Rammensee HG, Rieber EP. Generation of survivin-specific CD8+ T effector cells by dendritic cells pulsed with protein or selected peptides. Cancer Res. 2000;60:4845-9.
