Characterization and modulation of innate myeloid cells in hepatocellular carcinoma

Abstract:

Innate myeloid cells (tumor associated macrophages, myeloid derived suppressor cells) play a central role in creating an immune suppressive tumor environment, thus promoting local growth and metastasis of hepato-biliary malignancies. We propose to characterize and modulate myeloid lineage cells in murine models of hepatocellular carcinoma and in cells and tissue from patients with hepato-biliary malignancies. The final goal is to identify and validate novel therapeutic targets for a stroma-directed treatment of hepatic malignancies.

Principal investigators:

PD Dr. med. Martin Sprinzl, Franz
I. Medizinische Klinik und Poliklinik
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
Langenbeckstraße 1, 55131 Mainz
Phone: +49 (0)6131 17-4406
E-mail: martin.sprinzl@unimedizin-mainz.de
Web: http://www.unimedizin-mainz.de/1-med/patienten/mitarbeiter/portraits/sprinzl.html

Prof. Dr. med. Dr. rer. nat. Detlef Schuppan
Institut für Translationale Immunologie
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
Langenbeckstraße 1, 55131 Mainz
Phone: +49 (0)6131 17-7355/56
E-Mail: detlef.schuppan@unimedizin-mainz.de
Web: http://www.unimedizin-mainz.de/tim/head-office/weitere-informationen/schuppan.html?L=1

Postdoc:

Dr. Leonard Kaps

Doctoral candidates:

Christian Gosmann

Marie Kruchem

Dominik Siegl

Project-related publications:

Sprinzl MF, Galle PR (2014) Immune control in hepatocellular carcinoma development and progression: role of stromal cells. Sem Liv Dis 34: 376-388

Sprinzl MF, Puschnik A, Schlitter AM, Schad A, Ackermann K, Esposito I, Lang H, Galle PR, Weinmann A, Heikenwalder M, Protzer U (2015) Sorafenib inhibits macrophage-induced growth of hepatoma cells by interference with insulin-like growth factor-1 secretion. J Hepatol 62: 863-870

Sprinzl MF, Reisinger F, Puschnik A, Ringelhan M, Ackermann K, Hartmann D, Schiemann M, Weinmann A, Galle PR, Schuchmann M, Friess H, Otto G, Heikenwalder M, Protzer U (2013) Sorafenib perpetuates cellular anticancer effector functions by modulating the crosstalk between macrophages and natural killer cells. Hepatology 57: 2358-2368

Sprinzl MF, Russo C, Kittner J, Allgayer S, Grambihler A, Bartsch B, Weinmann A, Galle PR, Schuchmann M, Protzer U, Bauer T (2014) Hepatitis B virus-specific T-cell responses during IFN administration in a small cohort of chronic hepatitis B patients under nucleos(t)ide analogue treatment. J Viral Hep 21: 633-641

Dargel C, Bassani-Sternberg M, Hasreiter J, Zani F, Bockmann JH, Thiele F, Bohne F, Wisskirchen K, Wilde S, Sprinzl MF, Schendel DJ, Krackhardt AM, Uckert W, Wohlleber D, Schiemann M, Stemmer K, Heikenwälder M, Busch DH, Richter G, Mann M, Protzer U. (2015) T Cells Engineered to Express a T-Cell Receptor Specific for Glypican-3 to Recognize and Kill Hepatoma Cells In Vitro and in Mice. Gastroenterology. 149:1042-1052

Kwong GA, von Maltzahn G, Murugappan G, Abudayyeh O, Mo S, Papayannopoulos IA, Sverdlov DY, Liu SB, Warren AD, Popov Y, Schuppan D*, Bhatia SN (2013). Mass-encoded synthetic biomarkers for multiplexed urinary monitoring of disease. Nat Biotechnol 31:63-70 (*equal senior authorship)

Jiménez Calvente C, Sehgal A, Popov Y, Kim YO, Zevallos V, Sahin U, Diken M, Schuppan D (2015). Specific hepatic delivery of procollagen α1(I) small interfering RNA in lipid-like nanoparticles resolves liver fibrosis. Hepatology 62:1285-97

Leber N, Kaps L, Aslam M, Schupp J, Brose A, Schäffel D, Fischer K, Diken M, Strand D, Koynov K, Tuettenberg A, Nuhn L, Zentel R, Schuppan D (2016). SiRNA-mediated in vivo gene knockdown by acid-degradable cationic nanohydrogel particles. J Control Release 248:10-23

Tuettenberg A, Steinbrink K, Schuppan D (2016). Myeloid cells as orchestrators of the tumor microenvironment: novel targets for nanoparticular cancer therapy. Nanomedicine 11:2735-2751