GRK 2727:  Innate Immune Checkpoints in Cancer and Tissue Damage (InCheck)

• Subject Area: Microbiology, Virology and Immunology
• Term: since 2022
• Website: Homepage
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 445549683

Biological processes are controlled by balanced activating and inhibiting forces. If stimulatory signals prevail, cells become activated, whereas a dominance of inhibitory forces suppresses activation pathways. Within these pathways, roadblocks exist, so-called checkpoints, to interrupt ongoing pro-cesses and allow quality control. In the immune system, blocking of regulatory checkpoint circuits unleashes immune reactivity against invading pathogens and malignant cells, but can also promote activation, causing extensive tissue damage. In adaptive immunity, inhibitory checkpoint receptors on T-lymphocytes are well defined and exploited by checkpoint inhibitor therapies in cancer patients. Our knowledge of checkpoints in innate immune cells, however, is still in its infancy. The goal of GRK 2727 is to uncover checkpoints in innate immune cells at the transcriptional, posttranscriptional, metabolic and cell-surface receptor levels, and to validate their functions in cancer and conditions of tissue damage. We will focus on Natural Killer (NK) cells and monocytes/macrophages that function at the forefront of immune responses. We expect that the obtained mechanistic knowledge will be instru-mental for the design of innovative therapies of cancer and in conditions of tissue damage, where these checkpoints could be therapeutically blocked or fostered, respectively. Consortium members will benefit from complementary expertise in innate immunity, a common focus on complex immune processes, and from sharing cutting-edge experimental methods. At the educational level, GRK 2727 students will obtain extensive training in (innate) immunity in an InCheck-tailored program, including special lectures, science afternoons, dedicated workshops and hands-on training courses. To foster the interdisciplinary interaction between basic and translational science, the GRK 2727 will support tandem collaborations of PhD and MD students, working in the same lab. Presentation of thesis re-sults by our students at international conferences will further enhance the international visibility of GRK2727. Renowned experts from Vienna University and Karolinska Institute in Stockholm, both pres-tigious institutions with a long-standing record in innate immunity, will greatly contribute to GRK 2727 graduate education, as members of thesis advisory committees, as hosts for student lab-visits and during joint workshops.

• DFG Programme: Research Training Groups
• Applicant Institution: Ruprecht-Karls-Universität Heidelberg
• Participating Institution: Deutsches Krebsforschungszentrum (DKFZ)
• Spokesperson: Professorin Dr. Adelheid Cerwenka
• Participating Researchers: Privatdozentin Dr. Elke Burgermeister; Professor Dr. Matthias Ebert; Professor Dr. Florian Leuschner; Privatdozent Holger A. Lindner, Ph.D.; Professorin Dr. Sonja Loges; Professorin Dr. Ana Martin-Villalba; Professor Dr. Thomas Miethke; Professorin Dr. Martina Muckenthaler; Professorin Dr. Nina Papavasiliou; Professor Dr. Michael Platten; Dr. Katharina Sahm; Professor Dr. Lucas Schirmer; Dr. Johanna Schott; Professor Dr. Georg Stoecklin; Ana Stojanovic, Ph.D.; Professor Dr. Markus Weigand