Mechanisms of immune evasion by malignant glioma

Abstract:

Patients diagnosed with malignant glioma have a poor prognosis and usually die within twelve months post diagnosis. Recently, it has become evident that immune evasion is important for the progression of glioma. As the underlying molecular mechanisms are still poorly understood, we will investigate these mechanisms using in vivo mouse models of malignant glioma. Specifically, we will determine the general role of secreted factors, e.g., the epidermal growth factor-like protein 7 (EGFL7), for the attraction and repulsion of immune cell populations into the brain tumor mass, which we will visualise live and in vivo. Understanding brain tumor-mediated immune escape mechanisms will allow us to develop novel therapeutic strategies for malignant glioma.

Principal investigators:

Univ.-Prof. Dr. rer. nat. Dr. med. habil. Mirko H.H. Schmidt
Institut für Mikroskopische Anatomie und Neurobiologie (IMAN)
Universitätsmedizin der Johannes Gutenberg-Universität
Langenbeckstraße 1, 55131 Mainz
Phone: +49 (0)6131 17-8071
Email: mirko.schmidt@unimedizin-mainz.de
Web: http://www.unimedizin-mainz.de/iman/research-ag-schmidt.html

Univ.-Prof. Dr. med. Frauke Zipp
Klinik und Poliklinik für Neurologie
Universitätsmedizin der Johannes Gutenberg-Universität
Langenbeckstraße 1, 55131 Mainz
Phone: +49 (0)6131 17-7156
Email: frauke.zipp@unimedizin-mainz.de
Web: http://www.unimedizin-mainz.de/neurologie/startseite/startseite.html

Postdoc:

Ph.D. Ulrike Schumann

cand. Dr. rer. nat. Sebastian Seiferheld

Doctoral candidates:

Lynn Bitar

Project-related publications::

Bicker F, Vasic V, Horta G, Ortega F, Nolte H, Kavyanifar A, Keller S, Dudvarski Stankovic N, Harter PN, Benedito R, Lutz B, Bäuerle T, Hartwig J, Baumgart J, Krüger M, Radyushkin K, Alberi L, Berninger B, Schmidt MHH (2017) Neurovascular EGFL7 regulates subventricular neural stem cells, neurogenesis and olfactory perception. Nat Commun 8:15922

Dudvarski Stankovic N, Teodorczyk M, Ploen R, Zipp F, Schmidt MHH (2016) Microglia–blood vessel interactions: a double-edged sword in brain pathologies. Acta Neuropathol 131: 347-363

Dudvarski Stankovic N, Hoppmann N, Teodorczyk M, Kim EL, Bros M, Giese A, Zipp F§, Schmidt MHH§ (2016) No role of IFITM3 in brain tumor formation in vivo. Oncotarget, 7.52: 86388 (§equally contributing)

Jolivel V, Bicker F, Binamé F, Ploen R, Keller S, Gollan R, Jurek B, Birckenstock J, Poisa-Beiro L, Bruttger J, Opitz V, Thal SC, Waisman A, Bäuerle T, Schäfer MK, Zipp F§, Schmidt MHH§ (2015) Perivascular microglia promote blood vessel disintegration in the ischemic penumbra. Acta Neuropathol 129: 279-295 (§equally contributing)

Paterka M, Siffrin V, Voss JO, Werr J, Hoppmann N, Gollan R, Belikan P, Bruttger J, Birkenstock J, Jung S, Esplugues E, Yogev N, Flavell RA, Bopp T, Zipp F (2015) Gatekeeper role of brain antigen‐presenting CD11c+ cells in neuroinflammation. EMBO J 35:89-101

Liblau RS, Gonzalez-Dunia D, Wiendl H, Zipp F (2013) Neurons as targets for T cells in the nervous system. Trends Neurosci 36: 315-324

Nikolic I, Dudvarski Stankovic N, Bicker F, Meister J, Braun H, Awwad K, Baumgart J, Simon K, Thal SC, Patra C, Harter PN, Plate KH, Engel FB, Dimmeler S, Eble JA, Mittelbronn M, Schafer MK, Jungblut B, Chavakis E, Fleming I, Schmidt MHH (2013) EGFL7 ligates alphavbeta3 integrin to enhance vessel formation. Blood 121: 3041-3050

Roep BO, Buckner J, Sawcer S, Toes R, Zipp F (2012) The problems and promises of research into human immunology and autoimmune disease. Nature Med 18: 48-53

Siffrin V, Radbruch H, Glumm R, Niesner R, Paterka M, Herz J, Leuenberger T, Lehmann SM, Luenstedt SM, Rinnenthal JL, Laube G, Luche H, Lehnardt S, Fehling H, Griesbeck O, Zipp F (2010) In vivo imaging of partially reversible th17 cell-induced neuronal dysfunction in the course of encephalomyelitis. Immunity 33: 424-436