prof. Georges Leclercq (PhD)
Principal investigator - Laboratory of Experimental Immunology (UGent)
Full professor - Faculty of Medicine and Health Sciences, UGent
One part of our research focuses on the anti-cancer response of murine natural killer (NK) cells and intra-epithelial localized T cells. We have shown that part of these cells express the inhibitory receptor Ly49E, and that Ly49E is triggered by urokinase plasminogen activator. Urokinase plasminogen activator is a prognostic marker in a large variety of cancers, where high levels of uPA in tumor tissue predict poor outcome. Our aim is to study whether expression of the Ly49E receptor on NK cells and intra-epithelial localized T cells affects their in vivo immune response angainst cancer. If this is the case, uPA produced by cancer cells is not only advantageous for these cells by promoting their invasion and metastasis, but also because it is used as an escape mechanism from the host immune response.
In the second part of our research, we focus on human NK cells. NK cells have been shown to have high cytotoxic potential against various cancer cell types, and are currently used in the clinic for treatment of cancer patients. Whereas a lot is known regarding differentiation and function of murine NK cells, current knowledge regarding human NK cells is limited. Our aim is to reveal the role of several transcription factors in the differentiation of human hematopoietic stem cells into mature NK cells, and in the maintenance and function of mature NK cells. The ultimate aim is to attribute to improved NK-based cancer immunotherapy.
- The transcription factor ETS1 is an important regulator of human NK cell development and terminal differentiation. Blood. 2020. 136:288-298. doi:org/10.1182/blood.2020005204
- A murine intestinal intraepithelial NKp46-negative innate lymphoid cell population characterized by group 1 properties. Cell Reports 2017. 19: 1431-1443. doi:10.1016/j.celrep.2017.04.068.
- The role of Ly49E receptor expression on intraepithelial lymphocytes in intestinal cancer development and progression, Cancer Immunol. Immun. 2016. doi:10.1007/s00262-016-1894-6
- Expression of the inhibitory Ly49E receptor is not critically involved in the immune response against cutaneous, pulmonary or liver tumours, Scientific Reports. 2016. 6: 30564. doi:10.1038/srep30564.
- Differential Ly49e expression pathways in resting versus T cell receptor-activated intraepithelial γδ T cells, J. Immunol., 2013, 190: 1982–1990. doi:10.4049/jimmunol.1200354
- Inhibitory receptors specific for MHC class I educate murine NK cells but not CD8αα intestinal intraepithelial T lymphocytes, Blood, 2011, 118: 339-347. doi:10.1182/blood-2011-01-331124
- Continuous CD27 triggering in vivo strongly reduces natural killer cell numbers, Eur. J. Immunol., 2010, 40: 1107-1117. doi:10.1002/eji.200939251
- A role for Ly49A-MHC class I cis interaction for NK cell education, Immunity, 2009, 30: 337-347. doi:10.1016/j.immuni.2008.12.019.
- Ly49E-dependent inhibition of natural killer cells by urokinase plasminogen activator, Blood. 2008,112: 5046-5051. doi:10.1182/blood-2008-06-164350