SFB 1292:  Targeting convergent mechanisms of inefficient immunity in tumors and chronic infections

• Subject Area: Medicine ; Biology
• Term: since 2018
• Website: Homepage
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 318346496

Cancer and chronic infections evade the immune system by manipulating host defense mechanisms. Immunotherapies, such as checkpoint inhibitors, have been developed to target these mechanisms. However, durable responses remain limited due to the complex immunosuppressive environment in tumors and chronically infected tissues. The goal of the CRC 1292 is to identify and target convergent mechanisms underlying immune evasion and inefficient immunity in tumors and chronic infections. We aim to integrate disease-focused research with preclinical animal models and molecular systems immunology to dissect the pathophysiological processes underlying inefficient immunity. Key mechanisms contributing to inefficient immunity include antigenic camouflage, cytokine and soluble mediator modulation, and signal transduction cascade manipulation. Therapies targeting these pathways, such as monoclonal antibodies and cytokine traps, aim to restore proper immune function. We have made significant progress in deciphering the mechanisms of pH sensing in tissues and the role of coagulation proteases in regulating immune responses during viral infections. We have also investigated small molecules that affect signaling pathways, interfering with both the formation of metastasis and viral replication. Our research has identified shared molecular programs in tumor Treg cells, normal tissue adjacent to tumor Treg cells, Treg cells present in infected tissues, and healthy tissue Treg cells in mice and humans. We have also observed that the microbiome is essential for the produc-tion of basal levels of Type I Interferons, which are central to the functional activation of innate immune cells and subsequent priming of adaptive immune responses. Our findings have high potential for clinical translation and compatibility with existing immuno-therapy regimens. Several clinical trials have been initiated based on these results. We will continue to analyze the mechanisms with the potential to be relevant in both tumors and chronic infections, with the aim of generating a detailed map of shared and disease-specific immune escape checkpoints.

• DFG Programme: Collaborative Research Centres

Current projects

• 01 - Understanding the molecular mechanisms of polyamines in regulating regulatory T cell functional polarization in chronic infections and in tumors (Project Head Bopp, Tobias )
• 02 - TF-PAR signaling in viral infections (Project Heads Beling, Antje ;  Ruf, Wolfram )
• 05 - Signaling mechanisms regulating anti-tumor immunity and viral pathogenesis (Project Heads Ciesek, Sandra ;  Rajalingam, Krishnaraj )
• 08 - Mechanism and modulation of organ-specific therapy responses in metastatic melanoma (Project Heads Deppermann, Carsten ;  Kramer, Daniela ;  Schuppan, Detlef )
• 09 - Modulation of glioma-neuron networks by immune cells in malignant brain tumors (Project Heads Schmidt, Mirko H.H. ;  Zipp, Frauke )
• 10 - Elucidating the interplay between coagulation and pH in modulating antitumor immunity (Project Heads Graf, Ph.D., Claudine ;  Munir, Hafsa ;  Ruf, Wolfram )
• 11 - Transcriptional regulation and interactomes of viral immune evasion proteins (Project Heads Distler, Ute ;  Lemmermann, Niels ;  Reddehase, Matthias J. )
• 12 - Edited CAR effector cell therapy targeting adaptive resistance to therapeutic Menin-KMT2A chromatin complex disruption in leukemia (Project Heads Fulda, Simone ;  Kühn, Michael ;  Ullrich, Evelyn )
• 13 - Tonic type I interferon induction by the human gut microbiota and its role in infection and cancer (Project Heads Probst, Hans Christian ;  Schild, Hansjörg ;  Vieira-Silva, Ph.D., Sara )
• 15 - The crosstalk between B cells and myeloid cells during viral and parasitic infection (Project Heads von Stebut, Esther ;  Waisman, Ari )
• 16 - Reg3-mediated mechanisms in control of UPR and anti-tumor immunity (Project Heads Greten, Florian R. ;  Hövelmeyer, Nadine )
• 17 - Identification of blood circulating dietary nutrients to empower anti-tumor neoepitope specific TCR T cells (Project Heads Kreiter, Sebastian ;  Sahin, Ugur ;  Vascotto, Fulvia )
• 18 - Harnessing Metabolic Modulation of Tregs and Dendritic Cells to Enhance Immunotherapy Efficacy (Project Heads Berod, Ph.D., Luciana ;  Sparwasser, Tim Dominik )
• 19 - Controlling the suppressive and regeneration programs in tumor-resident tissue Treg cells (Project Heads Delacher, Michael ;  Marini, Federico )
• 21 - Synergizing Immune Effectors and Transcriptional Modulation for Enhanced Type-I Interferon Therapy in MPNs (Project Heads Muth, Sabine ;  Radsak, Markus P. ;  Sasca, Daniel )
• 22 - (Re)installing Cancer Immunity in Pancreatic Cancer and Cancers of the Upper GI Tract (Project Heads Gaida, Matthias ;  Türeci, Özlem )
• 24 - Impact of MHC-I Ligandome Quality Control on the adaptive immune response in cancer and chronic infection (Project Heads Dikic, Ivan ;  Schild, Hansjörg )
• 26 - The role of subcellular GPR65 signaling in immune cell function (Project Heads Bock, Andreas ;  Bohn, Toszka )
• IRTGMGK - Integrated Research Training Group (IRTG) (Project Heads Bopp, Tobias ;  Clausen, Björn ;  Hövelmeyer, Nadine ;  Kühn, Michael )
• Q01 - Integrated OMICS, Bioinformatics and Morpho-molecular Immunomonitoring Unit (Project Heads Albrecht, Christian ;  Bukur, Valesca ;  Gaida, Matthias ;  Imbusch, Charles ;  Tenzer, Stefan )
• Z02 - Central Task (Project Heads Bopp, Tobias ;  Schild, Hansjörg )

Completed projects

• 04 - Regulation of SAMHD1: impact on inflammation, viral replication and malignant diseases (Project Head König, Renate )
• 06 - Molecular T cell immunotherapy and inhibition of tumor immune escape mechanisms (Project Heads Munder, Markus ;  Theobald, Matthias )
• 07 - Defining the role of hepatocellular carcinoma-related epigenetic alterations driving immune evasion (Project Heads Marquardt, Jens U. ;  Strand, Susanne )
• 14 - Immunmodulation of cytomegalovirus latency and reactivation by regulatory T cells and dendritic cells (Project Heads Clausen, Björn ;  Holtappels, Rafaela )
• 20 - Mechanisms of IL-10 mediated tumor immune evasion in colorectal cancer development (Project Heads Clausen, Björn ;  Hövelmeyer, Nadine )

• Applicant Institution: Johannes Gutenberg-Universität Mainz
• Participating Institution: Georg-Speyer-Haus; Institut für Tumorbiologie und experimentelle Therapie; Deutsches Krebsforschungszentrum (DKFZ); Helmholtz-Institut für Translationale Onkologie Mainz (HI-TRON Mainz)
• Participating University: Charité - Universitätsmedizin Berlin; Goethe-Universität Frankfurt am Main; Universitätsklinikum Köln; Klinik für Dermatologie und Venerologie; Rheinische Friedrich-Wilhelms-Universität Bonn; Technische Universität Dresden
• Spokespersons: Professor Dr. Tobias Bopp; Professor Dr. Hansjörg Schild, until 12/2025