153. Latent cytomegalovirus infection enhances baseline anti-tumor cytotoxicity but impairs NK-cell responses to acute exercise through preferential expansion of NKG2C+ NK-cells in healthy humans

Abstract

Cytomegalovirus (CMV) infection markedly expands NKG2C+/NKG2A- NK-cells, which are potent killers of infected cells expressing the non-classical MHC molecule HLA-E. As HLA-E is overexpressed in several bloodborne malignancies, we examined the impact of latent CMV infection and acute exercise on NK-cell cytotoxic activity (NKCA) against a wide range of tumor target cells with varying levels of HLA-E expression. In resting blood, the expansion of NKG2C+ NK-cells with CMV was associated with strong anti-leukemia (K562) and anti-myeloma (U266) NKCA that was proportionate to the level of target cell HLA-E expression. NKCA against transfected (HLA-E-bright) 221.AEH cells was 3-times higher in those with CMV, but no effect of CMV was found on NKCA against HLA-E-negative 721.221 cells. Blocking the interaction between NKG2C and HLA-E completely eliminated the effect of CMV on NKCA against 221.AEH cells. Although NK-cells were redeployed in large numbers with exercise, NKG2C+ NK-cells were among the poorest responders of the NK-cell subsets to 30-min of cycling exercise. This contributed to a blunted exercise-induced redeployment of total NK-cells in those with CMV. Moreover, NKCA against U266 and 221.AEH target cells was enhanced during exercise recovery, but not in those with CMV. In conclusion, latent CMV infection enhances NKCA through preferential expansion of NKG2C+ NK-cells; however, these cells respond poorly to a single bout of exercise indicating that CMV may impair acute stress-induced immunosurveillance.