MICA-Expressing Monocytes Enhance Natural Killer Cell Fc Receptor-Mediated Antitumor Functions.
Campbell AR, Duggan MC, Suarez-Kelly LP, Bhave N, Opheim KS, McMichael EL, Trikha P, Parihar R, Luedke E, Lewis A, Yung B, Lee R, Raulet D, Tridandapani S, Groh V, Yu L, Yildiz V, Byrd JC, Caligiuri MA, Carson WE 3rd
Cancer Immunol Res 5 778-789 01/01/2017
Natural killer (NK) cells are large granular lymphocytes that promote the antitumor response via communication with other cell types in the tumor microenvironment. Previously, we have shown that NK cells secrete a profile of immune stimulatory factors (e.g., IFNγ, MIP-1α, and TNFα) in response to dual stimulation with the combination of antibody (Ab)-coated tumor cells and cytokines, such as IL12. We now demonstrate that this response is enhanced in the presence of autologous monocytes. Monocyte enhancement of NK cell activity was dependent on cell-to-cell contact as determined by a Transwell assay. It was hypothesized that NK cell effector functions against Ab-coated tumor cells were enhanced via binding of MICA on monocytes to NK cell NKG2D receptors. Strategies to block MICA-NKG2D interactions resulted in reductions in IFNγ production. Depletion of monocytesFull Text