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Focus of research
Dendritic cells and cancer immunotherapy
Cancer vaccines represent a form of immunotherapy. They have shown to be mainly well-tolerated and can promote long-term specific anti-tumor immune responses. Dendritic cells (DCs) as the most potent antigen-presenting cells are vital players in inducing, maintaining and regulating these immune responses and therefore represent a crucial component of vaccination. Approaches combining therapeutic cancer vaccine strategies with approved agents are being designed. This provides the opportunity to introduce cancer vaccines into treatment at an early point of disease before onset of severe immune exhaustion. However, a critical challenge in using therapeutic agents to promote cancer immunotherapy is that they potentially also influence immune cells in the tumor microenvironment, possibly further impairing their ability to mount immune responses to dying tumor cells.
Our group and others have previously demonstrated altered DC phenotype and impaired function by exposure to various therapeutic agents and we focus on elucidating the influence of further therapeutic drugs in order to identify optimal partners for DC-based immunotherapies.
Another scientific interest is the role of checkpoint molecules in hematological malignancies. In contrast to a variety of other cancers, immune checkpoint blockade, e. g. using blocking antibodies to the Programmed cell death protein 1 or its ligand to date has failed to achieve clinical efficacy e.g. in multiple myeloma. Here too, an exhausted immune system may be the reason for missing response. Even though DCs are dominant partners of T cells, the role of DCs in this setting is not well-characterized. We plan to further elucidate the role of checkpoint molecules in DCs for a possible targeted manipulation of T cell responses in the context of DC-based immunotherapies.
Schmidt M, Altdörfer V, Schnitte S, Fuchs AR, Kropp KN, Maurer S, Müller MR, Salih HR, Rittig SM, Grünebach F, Dörfel D. The Deubiquitinase Inhibitor b-AP15 and Its Effect on Phenotype and Function of Monocyte-Derived Dendritic Cells. Neoplasia. 2019 Jul;21(7):653-664.
Dörfel D, Lechner CJ, Joas S, Funk T, Gutknecht M, Salih J, Geiger J, Kropp KN, Maurer S, Müller MR, Kopp HG, Salih HR, Grünebach F, Rittig SM. The BCR-ABL inhibitor nilotinib influences phenotype and function of monocyte-derived human dendritic cells. Cancer Immunol Immunother. 2018 May;67(5):775-783.
Rittig SM, Haentschel M, Weimer KJ, Heine A, Müller MR, Brugger W, Horger MS, Maksimovic O, Stenzl A, Hoerr I, Rammensee HG, Holderried TA, Kanz L, Pascolo S, Brossart P. Long-term survival correlates with immunological responses in renal cell carcinoma patients treated with mRNA-based immunotherapy. Oncoimmunology. 2015 Oct 29;5(5):e1108511.
Gutknecht M, Geiger J, Joas S, Dörfel D, Salih HR, Müller MR, Grünebach F, Rittig SM. The transcription factor MITF is a critical regulator of GPNMB expression in dendritic cells. Cell Commun Signal. 2015 Mar 24;13:19.
Schwarzbich MA, Gutknecht M, Salih J, Salih HR, Brossart P, Rittig SM*, Grünebach F*. The immune inhibitory receptor osteoactivin is upregulated in monocyte-derived dendritic cells by BCR-ABL tyrosine kinase inhibitors. *equally contributed. Cancer Immunol Immunother. 2012 Feb;61(2):193-202.
Rittig SM*, Haentschel M*, Weimer KJ, Heine A, Muller MR, Brugger W, Horger MS, Maksimovic O, Stenzl A, Hoerr I, Rammensee HG, Holderried TA, Kanz L, Pascolo S, Brossart P. Intradermal vaccinations with RNA coding for TAA generate CD8+ and CD4+ immune responses and induce clinical benefit in vaccinated patients. *equally contributed Mol Ther. 2011 May;19(5):990-9.
Schmidt SM*, König T*, Bringmann A, Held S, von Schwarzenberg K, Heine A, Holderried TA, Stevanovic S, Grünebach F, Brossart P. Characterization of BAX inhibitor-1 as a novel leukemia-associated antigen. *equally contributed. Leukemia. 2009 Oct;23(10):1818-24.
Knodler A*, Schmidt SM*, Bringmann A, Weck MM, Brauer KM, Holderried TAW, Grunebach F, Brossart P. Post-transcriptional regulation of adapter molecules by IL-10 inhibits TLR mediated activation of antigen presenting cells. *equally contributed. Leukemia 2009 Mar;23(3):535-44.
Schmidt SM*, Schag K*, Muller MR, Weinschenk T, Appel S, Schoor O, Weck MM, Grunebach F, Kanz L, Stevanovic S, Rammensee HG, Brossart P. Induction of adipophilin-specific cytotoxic T lymphocytes using a novel HLA-A2-binding peptide that mediates tumor cell lysis. *equally contributed. Cancer Res. 2004 Feb 1;64(3):1164-70.
Schmidt SM, Schag K, Müller MR, Weck MM, Appel S, Kanz L, Grunebach F, Brossart P. Survivin is a shared tumor-associated antigen expressed in a broad variety of malignancies and recognized by specific cytotoxic T cells. Blood. 2003 Jul 15;102(2):571-6.
- Berlin Institute of Health (BIH)