Amelioration of natural killer cell function driven by invariant natural killer T cell activation in multiple myeloma

Publication date: Available online 20 October 2017
Source:Clinical Immunology
Author(s): Tomonori Iyoda, Satoru Yamasaki, Michihiro Hidaka, Fumio Kawano, Yu Abe, Kenshi Suzuki, Norimitsu Kadowaki, Kanako Shimizu, Shin-ichiro Fujii
NK cells represent a first line of defense, but are progressively dysregulated in multiple myeloma (MM) patients. To restore and facilitate their antitumor effect, NK cells are required in sufficient quantities and must be stimulated. We initially assessed the frequency of NKT and NK cells from 34 MM patients. Both of frequencies in PBMCs correlated with those in BMMNCs irrespective of low numbers of BMMNCs. Then, we assessed the adjunctive effect of NKT cell stimulation with CD1d and α-GalCer complex on the NK cells. The expression of NKG2D on CD56^dimCD16⁺ NK cells and DNAM-1 on CD56^brightCD16⁻ NK cells increased after NKT cell activation. Apparently, NK cell-mediated antitumor effects were dependent on NKG2D and DNAM-1 ligands on myeloma cells. Thus, NK cell function in patients could be ameliorated, beyond the effect of immunosuppression, by NKT cell activation. This NKT-driven NK cell therapy could represent a potential new target modality.



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