BOA1
Natural killer cell interaction with colorectal cancer lymph node metastases
Simon Lord, Tim Holmes, Yasser El-Sherbiny, Graham Cook
Leeds University, Leeds, UK
Natural killer (NK) cells have an innate ability to detect and destroy tumour cells and are believed to play an important role in controlling tumour progression in vivo. We have investigated the role of these cells in the recognition and killing of primary and metastatic colorectal cancer using a cell line model. Contrary to our expectations the metastatic cells were more susceptible to NK cell mediated killing, in vitro, than cells from the corresponding primary tumour. MHC class I molecules are known to inhibit NK cell activation and the metastatic cells expressed lower levels than the primary tumour. These experiments were performed using NK cells isolated from peripheral blood. There are two major NK cell subsets in peripheral blood, 90% of cells having a highly cytotoxic activity and 10% being poorly cytotoxic. In the lymph node the relative abundance of these populations is reversed. Selection of NK cells that mimic the poorly cytotoxic population in the lymph node confirmed that the metastatic cells were highly resistant to this population of NK cells.
These results suggest that the expression of tumour cell surface molecules that regulate NK cells are altered during metastasis and that the tissue in which the metastasis is resident strongly influences the likely outcome of attack by NK cells. Defining methods to boost the cytotoxicity of lymph node resident NK cells could tip the balance in favour of anti-tumour immune responses in a therapeutic setting.
