Targeting S100A8/S100A9 induced MDSCs in inflammatory disorders

Principal investigators: Sven Hermann, Thomas Vogl
Project number: CRC 1450 C03
Project term: 01/2021–12/2028

Immune-regulatory mechanisms limiting immunological responses are promising new therapeutic targets for chronic inflammatory diseases. This project will investigate to what extent the tetrameric form of the alarmin S100A8/S100A9 modulates the regulatory phenotype of MDSCs via CD69 in experimental models of arthritis and inflammatory tumour microenvironment. Multiscale imaging methods will be used to localize and study the interaction of MDSCs, S100A8/S100A9 and activated leukocytes in mouse models of arthritis and tumour xenografts over time and to evaluate the therapeutic potential of modulating the MDSC phenotype in arthritis.

Team

Principal investigators

Project members

Publications

The names of the principal investigators in our network have been bolded. Publications released prior to 2021, when funding for our network commenced, represent previous project-related work.

2023

Hoffmann E, Schache D, Höltke C, Soltwisch J, Niland S, Krähling T, Bergander K, Grewer M, Geyer C, Groeneweg L, Eble JA, Vogl T, Roth J, Heindel W, Maus B, Helfen A, Faber C, Wildgruber M, Gerwing M, Hoerr V. Multiparametric chemical exchange saturation transfer MRI detects metabolic changes in breast cancer following immunotherapy. J Transl Med 2023;21: 577. Abstract
Jorch SK, McNally A, Berger P, Wolf J, Kaiser K, Chetrusca Covash A, Robeck S, Pastau I, Fehler O, Jauch-Speer S-L, Hermann S, Schäfers M, Van Gorp H, Kanneganti A, Dehoorne J, Haerynck F, Penco F, Gattorno M, Chae JJ, Kubes P, Lamkanfi M, Wullaert A, Sperandio M, Vogl T, Roth J, Austermann J. Complex regulation of alarmins S100A8/A9 and secretion via Gasdermin-D pores exacerbates autoinflammation in Familial Mediterranean Fever. J Allergy Clin Immunol 2023Abstract
Pruenster M, Immler R, Roth J, Kuchler T, Bromberger T, Napoli M, Nussbaumer K, Rohwedder I, Wackerbarth LM, Piantoni C, Hennis K, Fink D, Kallabis S, Schroll T, Masgrau-Alsina S, Budke A, Liu W, Vestweber D, Wahl-Schott C, Roth J, Meissner F, Moser M, Vogl T, Hornung V, Broz P, Sperandio M. E-selectin-mediated rapid NLRP3 inflammasome activation regulates S100A8/S100A9 release from neutrophils via transient gasdermin D pore formation. Nat Immunol 2023;24: 2021-2031. Abstract
Song J, Deshpande T, Zhang X, Hannocks M-J, Lycke N, Cardell SL, Sorokin L. The extracellular matrix of lymph node reticular fibers modulates follicle border interactions and germinal center formation. iScience 2023;26: 106753. Abstract
von Wulffen M, Luehrmann V, Robeck S, Russo A, Fischer-Riepe L, van den Bosch M, van Lent P, Loser K, Gabrilovich DI, Hermann S, Roth J, Vogl T. S100A8/A9-alarmin promotes local myeloid-derived suppressor cell activation restricting severe autoimmune arthritis. Cell Rep 2023;42: 113006. Abstract
Wolf M, Joseph R, Austermann J, Scharrnbeck-Davis C, Hermann S, Roth J, Vogl T. S100A8/S100A9 Integrates F-Actin and Microtubule Dynamics to Prevent Uncontrolled Extravasation of Leukocytes. Biomedicines 2023;11Abstract

2022

Foray C, Barca C, Winkeler A, Wagner S, Hermann S, Schäfers M, Grauer OM, Zinnhardt B, Jacobs AH. Interrogating Glioma-Associated Microglia and Macrophage Dynamics Under CSF-1R Therapy with Multitracer In Vivo PET/MRI. J Nucl Med 2022;63: 1386-1393. Abstract
Helfen A, Rieß J, Fehler O, Stölting M, An Z, Kocman V, Schnepel A, Geyer C, Gerwing M, Masthoff M, Vogl T, Höltke C, Roth J, Ng T, Wildgruber M, Eisenblätter M. In vivo imaging of microenvironmental and anti-PD-L1-mediated dynamics in cancer using S100A8/S100A9 as an imaging biomarker. Neoplasia 2022;28: 100792. Abstract
Honold L, Austrup M, Faust A, Konken CP, Schwegmann K, Zinnhardt B, Daniliuc CG, Haufe G, Schäfers M, Kopka K, Hermann S. Towards Optimized Bioavailability of (99m)Tc-Labeled Barbiturates for Non-invasive Imaging of Matrix Metalloproteinase Activity. Mol Imaging Biol 2022;24: 434-443. Abstract
Rösner L, Konken CP, Depke DA, Rentmeister A, Schäfers M. Covalent labeling of immune cells. Curr Opin Chem Biol 2022;68: 102144. Abstract
Russo A, Schürmann H, Brandt M, Scholz K, Matos ALL, Grill D, Revenstorff J, Rembrink M, von Wulffen M, Fischer-Riepe L, Hanley PJ, Häcker H, Prünster M, Sanchez-Madrid F, Hermann S, Klotz L, Gerke V, Betz T, Vogl T, Roth J. Alarming and Calming: Opposing Roles of S100A8/S100A9 Dimers and Tetramers on Monocytes. Adv Sci (Weinh) 2022: e2201505. Abstract

2021

Barca C, Foray C, Hermann S, Herrlinger U, Remory I, Laoui D, Schäfers M, Grauer OM, Zinnhardt B, Jacobs AH. The Colony Stimulating Factor-1 Receptor (CSF-1R)-Mediated Regulation of Microglia/Macrophages as a Target for Neurological Disorders (Glioma, Stroke). Front Immunol 2021;12: 787307. Abstract
Depke DA, Konken CP, Rösner L, Hermann S, Schäfers M, Rentmeister A. A novel (18)F-labeled clickable substrate for targeted imaging of SNAP-tag expressing cells by PET in vivo. Chem Commun (Camb) 2021;57: 9850-9853. Abstract
Foray C, Valtorta S, Barca C, Winkeler A, Roll W, Müther M, Wagner S, Gardner ML, Hermann S, Schäfers M, Grauer OM, Moresco RM, Zinnhardt B, Jacobs AH. Imaging temozolomide-induced changes in the myeloid glioma microenvironment. Theranostics 2021;11: 2020-2033. Abstract

2020

Perego M, Tyurin VA, Tyurina YY, Yellets J, Nacarelli T, Lin C, Nefedova Y, Kossenkov A, Liu Q, Sreedhar S, Pass H, Roth J, Vogl T, Feldser D, Zhang R, Kagan VE, Gabrilovich DI. Reactivation of dormant tumor cells by modified lipids derived from stress-activated neutrophils. Sci Transl Med 2020;12Abstract
Zinnhardt B, Müther M, Roll W, Backhaus P, Jeibmann A, Foray C, Barca C, Döring C, Tavitian B, Dolle F, Weckesser M, Winkeler A, Hermann S, Wagner S, Wiendl H, Stummer W, Jacobs AH, Schäfers M, Grauer OM. TSPO imaging-guided characterization of the immunosuppressive myeloid tumor microenvironment in patients with malignant glioma. Neuro Oncol 2020;22: 1030-1043. Abstract

2019

Roll W, Markwardt NA, Masthoff M, Helfen A, Claussen J, Eisenblätter M, Hasenbach A, Hermann S, Karlas A, Wildgruber M, Ntziachristos V, Schäfers M. Multispectral Optoacoustic Tomography of Benign and Malignant Thyroid Disorders: A Pilot Study. J Nucl Med 2019;60: 1461-1466. Abstract

2018

Vogl T, Stratis A, Wixler V, Völler T, Thurainayagam S, Jorch SK, Zenker S, Dreiling A, Chakraborty D, Fröhling M, Paruzel P, Wehmeyer C, Hermann S, Papantonopoulou O, Geyer C, Loser K, Schäfers M, Ludwig S, Stoll M, Leanderson T, Schultze JL, König S, Pap T, Roth J. Autoinhibitory regulation of S100A8/S100A9 alarmin activity locally restricts sterile inflammation. J Clin Invest 2018;128: 1852-1866. Abstract
Völler T, Faust A, Roth J, Schäfers M, Vogl T, Hermann S. A Non-Peptidic S100A9 Specific Ligand for Optical Imaging of Phagocyte Activity In Vivo. Mol Imaging Biol 2018;20: 407-416. Abstract

2017

Eisenblaetter M, Flores-Borja F, Lee JJ, Wefers C, Smith H, Hueting R, Cooper MS, Blower PJ, Patel D, Rodriguez-Justo M, Milewicz H, Vogl T, Roth J, Tutt A, Schaeffter T, Ng T. Visualization of Tumor-Immune Interaction - Target-Specific Imaging of S100A8/A9 Reveals Pre-Metastatic Niche Establishment. Theranostics 2017;7: 2392-2401. Abstract

2014

Rossaint J, Herter JM, Van Aken H, Napirei M, Döring Y, Weber C, Soehnlein O, Zarbock A. Synchronized integrin engagement and chemokine activation is crucial in neutrophil extracellular trap-mediated sterile inflammation. Blood 2014;123: 2573-2584. Abstract