SFB 1335:  Aberrant Immune Signals in Cancer

• Subject Area: Medicine ; Biology
• Term: from 2018 to 2023
• Website: Homepage
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 360372040

The immune system has a pivotal role in cancer pathogenesis and biology, as well as in tumour therapy. Its unique ability to recognize cancer cells of various histological origins and to orchestrate protective immune responses for efficient tumour cell killing has been successfully harnessed for cancer immunotherapy, which dramatically advanced the prognosis of individual cancer patients. However, antitumour immune responses are frequently impaired or only short-lived. Furthermore, pathological immune signals in the microenvironment of cancer cells can even directly promote malignancy and actively subvert tumour immune surveillance. Furthermore, immune cells themselves can also be targets of malignant transformation, and leukaemia or lymphoma are frequently triggered by oncogenic mutations which affect immune receptor signalling modules. Collectively, we consider the pathological signals that originate within, or are mediated by immune cells, and which ultimately support or promote malignancy, as aberrant immune signals in cancer. Our interdisciplinary network of clinical and basic scientists with key expertise in immunology and oncology, explore how corrupted immune signals trigger the development of haematopoietic malignancies, drive tumour-promoting inflammation or mediate evasion from antitumour immunity. To this end, we focus on model malignancies of the haematopoietic system, gastrointestinal tract and skin, in scenarios where a link between deviated immune signalling and neoplastic growth has been established in clinical settings. Using relevant mouse models of human disease and patient-derived material, together with novel enabling technologies including advanced molecular and cellular immunology and tumour biology methods, genetic engineering, organoids and in vivo screening, as well as microbiome, metabolome and high-dimensional single-cell and spatio-molecular histopathological analyses, we aim to generate new knowledge that will ultimately lead to the design of novel strategies to target aberrant immune signals for better anti-cancer therapies.

• DFG Programme: Collaborative Research Centres

Completed projects

• P01 - Aberrant Immune Receptor Signalling in T-cell lymphoma (Project Head Ruland, Jürgen )
• P02 - Immune cell signalling during the transformation of CLL to Richter Syndrome (Project Head Buchner, Maike )
• P03 - Aberrant CXCR4 signaling in lymphoma (Project Head Keller, Ulrich )
• P04 - Aberrant Cathepsin S (CTSS) Activity in Follicular Lymphoma (Project Head Weigert, Oliver )
• P05 - Investigating common and distinct mechanisms of c-Rel and OTUD4 in lymphoma (Project Heads Fernández-Sáiz, Vanesa ;  Schmidt-Supprian, Marc )
• P06 - Role of ubiquitin networks in NF-κB driven B cell neoplasms (Project Head Bassermann, Florian )
• P07 - Functional impact of MALT1 protease activation in B cell lymphomagenesis (Project Head Krappmann, Ph.D., Daniel )
• P08 - Mechanisms of inflammatory BCL10 signalling in intestinal carcinogenesis (Project Heads Ruland, Jürgen ;  Schraml-Schotta, Ph.D., Barbara )
• P10 - Characterization of aberrant immune signals driven by inflammatory cell death in cancer (Project Head Jost, Philipp )
• P11 - Linking microbiota changes and lipid signalling to tumour risk in models of unfolded protein response-driven colonic tumorigenesis (Project Head Haller, Dirk )
• P12 - Inflammatory pathways in subtypes of intestinal cancer (Project Heads Meissner, Felix ;  Saur, Dieter )
• P13 - Functional mapping of Ras induced immune signalling components in intestinal cancer (Project Head Rad, Roland )
• P14 - Extracellular vesicles induced by innate immune pathways in cancer immunosurveillance (Project Heads Heidegger, Simon ;  Poeck, Hendrik )
• P15 - Differential regulation of RIPK3 in tumour stroma and cancer cells (Project Heads Hornung, Veit ;  Sun, Ph.D., Zhiqi )
• P16 - Dissecting the communication between immune and tumor cells with quantitative proteomics (Project Head Meissner, Felix )
• P17 - Control of lymphatic metastasis by immune education of melanoma (Project Head Biedermann, Tilo )
• P18 - Regulation of T cell antitumor immunity by tonicity signals from the tumor microenvironment (Project Head Zielinski, Christina )
• P19 - Control of TCR-signalling specificity to combat liver cancer in the context of immunotherapy (Project Head Heikenwälder, Mathias )
• Z01 - Histo-pathological and high-dimensional molecular characterization of cells and tissues (Project Heads Klughammer, Ph.D., Johanna ;  Steiger, Katja ;  Theis, Fabian ;  Weichert, Wilko )
• Z02 - Central Tasks (Project Head Ruland, Jürgen )

• Applicant Institution: Technische Universität München (TUM)
• Participating University: Ludwig-Maximilians-Universität München; Rheinische Friedrich-Wilhelms-Universität Bonn; Universität Regensburg
• Participating Institution: Deutsches Krebsforschungszentrum (DKFZ); Forschungsschwerpunkt Infektion, Entzündung und Krebs; Abteilung Chronische Entzündung und Krebs (F180); Max-Planck-Institut für Biochemie ; Arbeitsgruppe Zellbiochemie; Helmholtz Zentrum München; Deutsches Forschungszentrum für Gesundheit und Umwelt
• Spokesperson: Professor Dr. Jürgen Ruland