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Updated: May 28, 2025

Flow Cytometry-based Assay for the Monitoring of NK Cell Functions
Published on: October 30, 2016
NK Cell Immaturity and NKp30 Expression Positively Correlate with Clinical Outcome in Multiple Myeloma Patients from
Marine Villard1, Sébastien Viel1,2, Lionel Karlin3
1CIRI, Centre International de Recherche en Infectiologie, Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France.
Abstract:
Multiple myeloma (MM) is a proliferation of tumoral plasma cells that is still incurable. Natural killer (NK) cells can recognize and kill MM cells in vitro. However, previous literature suggests an alteration of NK cell function in MM patients. To further evaluate this point, we used multi-parametric flow cytometry to monitor NK cell phenotype in bone marrow samples at diagnosis of MM, taking advantage of the IFM2009 trial and associated samples. Our results show an increase in the frequency of NK cells in MM patients. A detailed analysis of NK cell phenotype showed a decreased expression of terminal maturation markers such as KLRG1 or CD57 and an increased expression of CD56bright/tissue resident markers among NK cells from MM patients. The extent of these alterations is even more pronounced as the ISS score increases in patients. Finally, a favorable clinical evolution correlates with NK cell immaturity, on the one hand, and with the level of NKp30, a receptor more expressed in immature NK cells on the other hand. Altogether, these data suggest that immature and resident NK cells are particularly involved in the anti-myeloma response, notably via NKp30, which could pave the way for future therapeutic strategies.
Insights
Natural killer (NK) cells show altered immaturity and tissue-resident markers in multiple myeloma (MM) patients. This immaturity, particularly via NKp30, correlates with favorable clinical outcomes, suggesting therapeutic potential.
Area of Science:
- Immunology
- Hematology
- Oncology
Background:
- Multiple myeloma (MM) is an incurable plasma cell malignancy.
- Natural killer (NK) cells exhibit anti-myeloma activity in vitro.
- NK cell function is reportedly altered in MM patients.
Purpose of the Study:
- To investigate NK cell phenotype and function in newly diagnosed MM patients.
- To correlate NK cell characteristics with disease severity and clinical outcomes.
Main Methods:
- Multi-parametric flow cytometry analysis of bone marrow samples from MM patients.
- Utilized samples from the IFM2009 clinical trial.
- Monitored NK cell frequency, maturation markers (KLRG1, CD57), and CD56 expression.
Main Results:
- MM patients exhibit increased NK cell frequency.
- NK cells display decreased expression of terminal maturation markers (KLRG1, CD57).
- Increased CD56bright/tissue-resident NK cells and NKp30 expression observed, correlating with lower ISS scores and favorable clinical evolution.
Conclusions:
- Immature and tissue-resident NK cells, particularly via NKp30, are implicated in anti-myeloma responses.
- NK cell immaturity and NKp30 expression are associated with favorable clinical outcomes in MM.
- These findings suggest potential therapeutic strategies targeting NK cells in multiple myeloma.

