NK cells and anti-tumor immune responses

ZWIRNER, NORBERTO WALTER

Buenos Aires

Simposio; New insights in Cellular and Molecular Interactions in the Immune Response; 2009

Laboratorio de Investigación en el Sistema Inmune (LISIN), Facultad de Ciencias Exactas, Universidad Nacional de La Plata

Natural killer (NK) cells trigger cytotoxicity and interferon (IFN)-g secretion on engagement of the natural-killer group (NKG)2D receptor or members of the natural cytotoxicity receptor (NCR) family, such as NKp46, by ligands expressed on tumour cells. However, it remains unknown whether T cells can regulate NK cell-mediated anti-tumour responses. Here, we investigated the early events occurring during T cell–tumour cell interactions, and their impact on NK cell functions. We observed that on co-culture with some melanomas, activated CD4þ T cells promoted degranulation, and NKG2D- and NKp46-dependent IFN-g secretion by NK cells, probably owing to the capture of NKG2D and NKp46 ligands from the tumour-cell surface (trogocytosis). This effect was observed in CD4þ, CD8þ and resting T cells, which showed substantial amounts of cell surface major histocompatibility complex class I chain-relatedprotein A on co-culture with tumour cells. Our findings identify a new, so far, unrecognized mechanism by which effector T cells support NK cell function through the capture of specific tumour ligands with profound implications at the crossroad of innate and adaptive immunity.