Inhibitory receptor repertoire of anti-tumoral NK cells in mouse MHC-I-deficient cancers

• Applicant: Dr. Gabriela Wiedemann
• Subject Area: Hematology, Oncology ; Immunology
• Term: from 2017 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 389276769

Natural killer cells (NK cells) are lymphoid cells of the innate immune system. They have been identified by their capacity to rapidly kill tumor cells or virus-infected cells without prior sensitization. For target cell recognition, NK cells are endowed with an abundant repertoire of activating and inhibiting receptors, which allows them to recognize stress ligands and MHC class I (MHC-I) downregulation on infected cells and cancer cells. Upon recognition, NK cells are able to rapidly kill their targets. In the past decade, T cell-targeted immunological cancer therapies have shown great success and many have quickly entered FDA approval. However, a significant number of cancers downregulate MHC-I on their surface to escape T cell mediated killing. As NK cells effectively recognize and eliminate these MHC-I low tumor cells, these tumor types are specifically prone to NK cell therapies. This project aims at investigating NK cell subsets with a high potential of killing MHC-I low tumors and increasing their therapeutic potential. By analyzing the dynamic phenotypic changes of NK cells in MHC-I low tumors, a tumor-reactive NK cell subset was defined. Now, strategies to expand this subset and to increase its cytotoxicity will be examined. This project is an important step towards the development of clinical cancer therapies exploiting the cytotoxic capacities of NK cells.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Joseph C. Sun, Ph.D.