Plastizität von Natürlichen Killerzellen bei Krebserkrankungen
Zusammenfassung der Projektergebnisse
Metastasis is the most prominent cause of death in cancer patients. It is an organized course in which tumour cells are released from the primary site into the circulation, and these circulating tumour cells establish new tumours at different sites. The control of circulating tumour cells depends highly on functional NK cells. Our mouse model study showed how FcRγ educates NK cells to react and mount effector functions upon tumour cell recognition, which was required to limit metastasis. We also identified that the lack of education in FcRγ–/– NK cells was not permanent, and a low dose of IL-15 treatment rescued them from hyporeactivity to control tumour growth. The finding of this project highlights that cancer patients whose NK cells are present in a hyporesponsive state can benefit from a low dose of IL-2 or IL-15 treatment by promoting NK cell sensitivity to tumour cells. Cytomegalovirus (CMV) infection in humans induces the generation of adaptive-like NK cells, which are FcRγ negative (FcRγ–). FcRγ– NK cells constitute up to 70% of the total peripheral blood NK cell population in one-third of healthy CMV seropositive individuals. How FcRγ– NK cell population impacts cancer control is poorly known. Some in vitro studies revealed that FcRγ– NK cells are less efficient in targeting tumour cells. Whether this is linked to NK cell education by CD244 is not known. To move forward with this project, we are also interested in understanding the role of FcRγ in human settings. It would also be interesting for translational purposes if the functionality of FcRγ– NK cells in CMV seropositive cancer patients can be enhanced by targeting the education pathway with cytokine treatment. Further, we are working on understanding the mechanism underlying FcRγ dependent CD244 expression and reversal of FcRγ–/– NK cell hypo-reactivity upon cytokines treatment.
Projektbezogene Publikationen (Auswahl)
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Innate myeloid cells in the tumor microenvironment. Current Opinion in Immunology, 69, 18-28.
Duhan, Vikas & Smyth, Mark J.
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Editorial: Natural killer cell plasticity and diversity in antiviral immunity. Frontiers in Immunology, 14.
Krebs, Philippe; Peng, Hui & Duhan, Vikas
