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Article

High Expression of Cannabinoid Receptor 2 on Cytokine-Induced Killer Cells and Multiple Myeloma Cells

Department of Integrated Oncology, Center for Integrated Oncology (CIO), University Hospital Bonn, 53127 Bonn, Germany
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Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(11), 3800; https://doi.org/10.3390/ijms21113800
Received: 3 April 2020 / Revised: 26 May 2020 / Accepted: 26 May 2020 / Published: 27 May 2020
(This article belongs to the Special Issue Cytokines/Chemokines in Cancer Metastasis)
Multiple myeloma (MM) is characterized by aberrant bone marrow plasma cell (PC) proliferation and is one of the most common hematological malignancies. The potential effect of cannabinoids on the immune system and hematological malignancies has been poorly characterized. Cannabidiol (CBD) may be used to treat various diseases. CBD is known to exert immunomodulatory effects through the activation of cannabinoid receptor 2 (CB2), which is expressed in high levels in the hematopoietic system. Cytokine-induced killer (CIK) cells are a heterogeneous population of polyclonal T lymphocytes obtained via ex vivo sequential incubation of peripheral blood mononuclear cells (PBMCs) with interferon-γ (IFN-γ), anti CD3 monoclonal antibody, and IL-2. They are characterized by the expression of CD3+ and CD56+, which are surface markers common to T lymphocytes and natural killer (NK) cells. CIK cells are mainly used in hematological patients who suffer relapse after allogeneic transplantation. Here, we investigated their antitumor effect in combination with pure cannabidiol in KMS-12 MM cells by lactate dehydrogenase LDH cytotoxicity assay, CCK-8 assay, and flow cytometry analysis. The surface and intracellular CB2 expressions on CIK cells and on KMS-12 and U-266 MM cell lines were also detected by flow cytometry. Our findings confirm that the CB2 receptor is highly expressed on CIK cells as well as on MM cells. CBD was able to decrease the viability of tumor cells and can have a protective role for CIK cells. It also inhibits the cytotoxic activity of CIKs against MM at high concentrations, so in view of a clinical perspective, it has to be considered that the lower concentration of 1 µM can be used in combination with CIK cells. Further studies will be required to address the mechanism of CBD modulation of CIK cells in more detail. View Full-Text
Keywords: cannabidiol; adoptive cellular immunotherapy; multiple myeloma; cytokine-induced killer cells; endocannabinoid system cannabidiol; adoptive cellular immunotherapy; multiple myeloma; cytokine-induced killer cells; endocannabinoid system
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MDPI and ACS Style

Garofano, F.; Schmidt-Wolf, I.G.H. High Expression of Cannabinoid Receptor 2 on Cytokine-Induced Killer Cells and Multiple Myeloma Cells. Int. J. Mol. Sci. 2020, 21, 3800. https://doi.org/10.3390/ijms21113800

AMA Style

Garofano F, Schmidt-Wolf IGH. High Expression of Cannabinoid Receptor 2 on Cytokine-Induced Killer Cells and Multiple Myeloma Cells. International Journal of Molecular Sciences. 2020; 21(11):3800. https://doi.org/10.3390/ijms21113800

Chicago/Turabian Style

Garofano, Francesca, and Ingo G.H. Schmidt-Wolf. 2020. "High Expression of Cannabinoid Receptor 2 on Cytokine-Induced Killer Cells and Multiple Myeloma Cells" International Journal of Molecular Sciences 21, no. 11: 3800. https://doi.org/10.3390/ijms21113800

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