Immunotherapy Brain Tumor Models

Despite a strict control of immune processes in the central nervous system (CNS), CNS immunity is off balance during autoimmune diseases and in CNS tumors such as gliomas or brain metastases where active immunosuppression takes place. Despite success in other solid tumors, immunotherapies such as checkpoint inhibition (CPI) have not achieved sufficient immune re-activation in brain tumors.

The focus of the team is to understand the complex mechanisms which lay behind a response or the resistance to cancer immunotherapies such as CPI, with the commitment to explore and exploit targets for improvement of clinical outcome. Previous data suggest a critical role for the myeloid compartment including tumor-associated macrophages (TAM), interacting with T effector cells, which we are currently looking at in detail to dissect immune microenvironmental determinants that shape a responsive phenotype.
Our research is driven by clinical data-based hypotheses, which we probe in various – mostly immunocompetent – genetic mouse models.

• Theresa Bunse, PhD - Team leader
• Dennis Agardy, M.Sc - PhD student
• Julia Gellert, MD student
• Verena Turco - MD student
• Sarwar Mustafa - MD student 

• Gellert J, Agardy DA, Kumar S,  Kourtesakis S,  Boschert T, Jähne K,  Breckwoldt MO, Bunse L, Wick W, Davies MA, Platten M, Bunse T. Tumoral Interferon Beta Induces an Immune-Stimulatory Phenotype in Tumor-Associated Macrophages in Melanoma Brain Metastases. Cancer Res Commun. 2024 Aug 1;4(8):2189-2202. 
• Hunger J, Schregel K, Boztepe B, Agardy D, Turco V, Karimian-Jazi K, Weidenfeld I, Streibel Y, Fischer M, Sturm V, Santarella-Mellwig R, Kilian M, Jähne K, Sahm K, Wick W, Bunse L, Heiland S, Bunse T, Bendszus M, Platten M, Breckwoldt MO. In vivo nanoparticle-based T cell imaging can predict therapy response towards adoptive T cell therapy in experimental glioma. Theranostics (2023)
• Turco V, Pfleiderer K, Hunger J, Horvat N, Karimian-Jazi K, Schregel K, Fischer M,  Brugnara G, Jähne K, Streibel Y, Sturm V, Nguyen D, Altamura S, Agardy D, Soni S, Alsasa A, Bunse T, Schlesner M, Muckenthaler M, Weissleder R, Wick W, Heiland S, Vollmuth P, Bendszus M, Rodell C, Breckwoldt M, and Platten M. T cell-independent eradication of experimental glioma by intravenous TLR7/8-agonist-loaded nanoparticles. Nature communications. (2023)
• Platten M, Bunse L, Wick A, Bunse T, Le Cornet L, Harting I, Sahm F, Sanghvi K, Tan CL, Poschke I, Green E, Justesen S, Behrens GA, Breckwoldt M, Freitag A, Rother LM, Schmitt A, Schnell O, Hense J, Misch M, Krex D, Stevanovic S, Tabatabai G, Steinbach JP, Bendszus M, von Deimling A, Schmitt M, Wick W. A vaccine targeting mutant IDH1 in newly diagnosed glioma. Nature. (2021)
• Friedrich M*, Sankowski R*, Bunse L*, Kilian M, Green E, Ramallo-Guevara C, Pusch S, Poschet G, Sanghvi K, Hahn M, Bunse T, Münch P, Sonner JK, von Landenberg A, Cichon F, Aslan K, Trobisch T, Schirmer L, Abu-Sammour D, Kessler T, Ratliff M, Schrimpf D, Sahm F, Hopf C, Heiland DH, Schnell O, Beck J, Böttcher C, Fernandez-Zapata C, Priller J, Heiland S, Gutcher I, Quintana FJ, von Deimling A, Wick W, Prinz M*, Platten M*. Tryptophan metabolism drives dynamic immunosuppressive myeloid states in IDH-mutant gliomas. Nature Cancer. (2021)
• Aslan K, Turco V, Blobner J, Sonner JK, Liuzzi AR, Núñez N, De Feo D, Kickingereder P, Fischer M, Green E, Sadik A, Friedrich M, Sanghvi K, Killian M, Cichon F, Wolf L, Jähne K, von Landenberg A, Bunse L, Sahm F, Schrimpf D, Meyer J, Alexander A, Brugnara G, Röth R, Nisler B, von Deimling A, Opitz C, Breckwoldt MO, Heiland S, Bendszus M, Wick W, Becher B und Platten M. Heterogeneity of response to immune checkpoint blockade in syngeneic hypermutated experimental gliomas. Nat Commun. 2020
  
• Sonner JK, Keil M, Falk-Paulsen M, Mishra N, Rehman A, Kramer M, Deumelandt K, Röwe J, Sanghvi K, Wolf L, von Landenberg A, Wolff H, Bharti R, Oezen I, Lanz TV, Wanke F, Tang Y, Brandao I, Mohapatra SR, Epping L, Grill A, Röth R, Niesler B, Meuth SG, Opitz CA, Okun JG, Reinhardt C, Kurschus FC, Wick W, Bode HB, Rosenstiel P, Platten M. Dietary tryptophan links encephalogenicity of autoreactive T cells with gut microbial ecology. Nat Commun. 2019
• Bunse L*, Pusch S*, Bunse T*, Sahm F, Sanghvi K, Friedrich M, Alansary D, Sonner JK, Green E, Deumelandt K, Kilian M, Neftel C, Uhlig S, Kessler T, von Landenberg A, Berghoff AS, Marsh K, Steadman M, Zhu D, Nicolay B, Wiestler B, Breckwoldt MO, Al-Ali R, Karcher-Bausch S, Bozza M, Oezen I, Kramer M, Meyer J, Habel A, Poschet G, Weller M, Preusser M, Nadji-Ohl M, Thon N, Burger M, Harter P, Ratliff M, Harbottle R, Benner A, Schrimpf D, Okun J, Herold-Mende CM, Turcan S, Kaulfuss S, Hess-Stumpp H, Bieback K, Cahill DP, Plate KH, Hänggi D, Dorsch M, Suva M, Niemeyer BA, von Deimling A, Wick W, Platten M. Suppression of antitumor T cell immunity by the oncometabolite R-2-hydroxyglutarate. Nat. Med. 2018 *Authors contributed equally
• Keil M, Sonner JK, Lanz TV, Oezen I, Bunse T, Bittner S, Meyer HV, Meuth SG, Wick W, Platten M. General control non-derepressible 2 (GCN2) in T cells controls disease progression of autoimmune neuroinflammation. J Neuroimmunol. 2016
• Bunse L*, Schumacher T*, Sahm F*, Pusch S, Oezen I, Wiestler B, Gonzalez M, Osswald M, Capper D, von Deimling A, Wick W, Platten M. In situ proximity ligation assay evaluates presentation of mutant isocitrate dehydrogenase 1 in gliomas. J Clin Invest. 2015 *Authors contributed equally.
• Schumacher T*, Bunse L*, Pusch S, Sahm F, Wiestler B, Quandt J, Menn O, Osswald M, Oezen I, Ott M, Keil M, Balß J, Grabowska AK, Vogler I, Diekmann J, Trautwein N, Eichmüller SB, Okun J, Stevanović S, Riemer AB, Sahin U, Friese MA, Beckhove P, von Deimling A, Wick W, Platten M. A vaccine targeting mutant IDH1 induces antitumor immunity. Nature. 2014 *Authors contributed equally.
• Opitz CA*, Litzenburger UM*, Sahm F, Ott M, Tritschler I, Trump S, Schumacher T, Jestaedt L, Schrenk D, Weller M, Jugold M, Guillemin GJ, Miller CL, Lutz C, Radlwimmer B, Lehman I, von Deimling A, Wick W, Platten M. An endogenous ligand of the human aryl hydrocarbon receptor. Nature. 2011 *Authors contributed equally.