Amelioration of NK cell function driven by Vα24+ invariant NKT cell activation in multiple myeloma.

Abstract

NK cells represent a first line of immune 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 proportions of NKT and NK cells in 34 MM patients. The frequencies of both in PBMC populations correlated with those in BMMNCs irrespective of low BMMNC numbers. We then assessed the adjunctive effect of stimulating NKT cells with CD1d and α-GalCer complexes on the NK cells. The expression of NKG2D on CD56dimCD16+ NK cells and DNAM-1 on CD56brightCD16- NK cells increased after NKT cell activation. Apparently, NK cell-mediated anti-tumor 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 treatment modality.

• Authors: Tomonori Iyoda, Satoru Yamasaki, Michihiro Hidaka, Fumio Kawano, Yu Abe, Kenshi Suzuki, Norimitsu Kadowaki, Kanako Shimizu, Shin-Ichiro Fujii
• Journal: Clinical immunology (Orlando, Fla.) (Clin Immunol) Vol. 187 Pg. 76-84 (02 2018) ISSN: 1521-7035 [Electronic] United States
• PMID: 29061445 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• Antigens, CD1d
• Antigens, Differentiation, T-Lymphocyte
• Antineoplastic Agents
• CD1D protein, human
• CD226 antigen
• Galactosylceramides
• Glucocorticoids
• KLRK1 protein, human
• NK Cell Lectin-Like Receptor Subfamily K
• Receptors, Antigen, T-Cell
• Valpha24 protein, human
• alpha-galactosylceramide

Topics

• Adult
• Aged
• Aged, 80 and over
• Antigens, CD1d (pharmacology)
• Antigens, Differentiation, T-Lymphocyte (drug effects, metabolism)
• Antineoplastic Agents (therapeutic use)
• Female
• Galactosylceramides (pharmacology)
• Glucocorticoids (therapeutic use)
• Humans
• Killer Cells, Natural (drug effects, immunology)
• Lymphocyte Activation
• Male
• Middle Aged
• Multiple Myeloma (drug therapy, immunology)
• NK Cell Lectin-Like Receptor Subfamily K (drug effects, metabolism)
• Natural Killer T-Cells (drug effects, immunology)
• Receptors, Antigen, T-Cell (immunology)