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Decreased CD161 activating and increased CD158a inhibitory receptor expression on NK cells underlies impaired NK cell cytotoxicity in patients with multiple myeloma
  1. Gordana Konjević1,2,
  2. Ana Vuletić1,
  3. Katarina Mirjačić Martinović1,
  4. Nataša Colović2,3,
  5. Milica Čolović2,
  6. Vladimir Jurišić4
  1. 1Department of Experimental Oncology, Institute of Oncology and Radiology of Serbia, Belgrade, Serbia
  2. 2Faculty of Medicine, University of Belgrade, Belgrade, Serbia
  3. 3Institute of Hematology, Clinical Center Serbia, Belgrade, Serbia
  4. 4Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia
  1. Correspondence to Professor Dr Vladimir Jurišić, University of Kragujevac, Faculty of Medical Sciences, Svetozara Marković, 69, Kragujevac 34000, Serbia; vdvd{at}


Aim As innate immune cells natural killer (NK), NK-like T and CTLγδ are important in antitumour response in multiple myeloma (MM), the aim of this study was to investigate some functional and phenotypical characteristics of these cells in MM.

Methods 29 patients with MM prior to therapy, in clinical stage I-III and 15 healthy controls (HCs) were investigated. Percent of immune cells in peripheral blood, NK cell activity, expression of activating (CD161) and inhibitory (CD158a, CD158b) NK cell receptors on CD3CD16+ NK cells were evaluated using 51-chromium-release assay and by flow cytometry. Production of interleukin (IL) 2 and tumour necrosis factor (TNF)α was analysed in supernatants from in vitro activated peripheral blood mononuclear cells.

Results In patients with MM the percent of NK cells and their two subsets did not differ from controls, while NK-like T and CTLγδ cells were significantly decreased. Significant impairment of NK cell cytotoxicity, CD107a expression and interferon γ intracellular level was also shown. There was a significant decrease in CD161 and an increase in CD158a receptor expression on NK cells in these patients. Also IL-2 production was lowest in clinical stage III. However, TNF-α production did not differ between patients and HCs.

Conclusions Altered expression of CD161 activating and CD158a KIR inhibitory receptor is responsible for impaired antitumour activity of NK cells in MM patients. These new biomarkers may be helpful for patient selection for immunotherapy with cytokines, and novel KIR blocking monoclonal antibodies that enhance NK cell antimyeloma activity and provide clinical benefit.


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  • Handling editor Mary Frances McMullin

  • Contributors GK, VJ, AV, KMM and MC designed the study, interpreted the data and wrote the manuscript. AV and KMM performed the NK cell cytotoxicity assay, flow cytometric analyses and ELISA assays.

  • Funding This work was supported by the grants of the Ministry of Education, Science and Technological Development of the Republic of Serbia (number 175056).

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval Ethical committee of the Institute of Oncology and Radiology of Serbia.

  • Provenance and peer review Not commissioned; externally peer reviewed.