Division of Molecular Immunology
Prof. Dr. Bernd Arnold
The Division of Molecular Immunology investigates basic mechanisms that are important for immunological tumor rejection with the aim to exploit this knowledge for the development of novel immunotherapeutic strategies. Our research groups focus on the following topics:
Antigen presentation: For successful destruction of tumor cells T lymphocytes need to be activated by dendritic cells presenting tumor antigens. Therefore, we are studying homeostasis and stimulatory capacity of dendritic cells and measure the precise biophysical interaction forces between antigen-presenting cells and T cells.
Peripheral tolerance: T lymphocytes are often rendered tolerant by tumors and, therefore, fail to attack the tumor. By investigating the molecular pathways leading to tolerance induction we identified a novel immune-modulator, Dickkopf-3, that can down-regulate T cell responses and may represent a novel tumor escape mechanism.
Tumor microenvironment: The tumor vasculature can restrict the access of T lymphocytes into the tumor, thereby preventing tumor eradication. We succeeded in strongly improving infiltration and tumor rejection by strategies that modulate the tumor microenvironment, including local irradiation, efficient depletion of regulatory T cells, and targeting of vasculature-associated genes. These strategies will be translated into the clinic.
The Division of Molecular Immunology will continue to investigate basic mechanisms that are crucial for immunological tumor rejection. We are focusing on the following aims:
Peripheral tolerance: Tissues particularly sensitive to inflammatory damage, like the brain and the eye, create an immune-suppressive microenvironment to limit immune responses. Likewise, developing tumors can generate a tolerogenic milieu, which facilitates tumor progression and antagonizes the efficacy of vaccination strategies. Our understanding of the key cellular and molecular players responsible for the induction and maintenance of tolerance is yet to be complete. Therefore, we will address the molecular basis of immune silencing by healthy organs and tumor cells and will focus on the identification of new molecular targets suitable for therapeutic reprogramming of the immune system.
Tumor microenvironment: Our studies show that T cell homing into tumors can be increased by a number of strategies all of which result in normalization of the tumor vasculature. Thus, normalization is likely to play a major role in T cell infiltration, which is a prerequisite for tumor rejection. Therefore, we will analyze the cellular and molecular mechanisms resulting in modulation of the tumor microenvironment, vessel normalization, and T cell infiltration. Identification of factors enhancing T cell infiltration will have important implications for clinical immunotherapy.
Miloud T, Fiegler N, Suffner J, Hämmerling GJ, Garbi N. Organ-specific cellular requirements for in vivo dendritic cell generation. J. Immunol. 188(3):1125-1135, 2012
Papatriantafyllou M, Moldenhauer G, Ludwig J, Tafuri A, Garbi N, Hollmann G, Küblbeck G, Klevenz A, Schmitt S, Pougialis G, Niehrs C, Gröne HJ, Hämmerling GJ, Arnold B, Oelert T. Dickkopf-3, an immune-modulator in peripheral CD8 T cell tolerance. Proc Natl Acad Sci USA 109(5):1631-1636, 2012
Hamzah J, Jugold M, Kiessling F, Rigby P, Manzur M, Marti HH, Rabie T, Kaden S, Gröne HJ, Hämmerling GJ, Arnold B, Ganss R. Vascular normalization in RGS5-deficient tumors promotes immune destruction. Nature 453(7193):410-414, 2008
Hochweller K, Wabnitz GH, Samstag Y, Suffner J, Hämmerling GJ, Garbi N. Dendritic cells control T cell tonic signalling required for responsiveness to foreign antigen. Proc.Natl.Acad.Sci. 107(13):5931-5936, 2010