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Wang, F. ; Bashiri Dezfouli, A.* ; Multhoff, G.*

The immunomodulatory effects of cannabidiol on Hsp70-activated NK cells and tumor target cells.

Mol. Immunol. 174, DOI: 10.1016/j.molimm.2024.07.008 (2024)
Verlagsversion DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
BACKGROUND: Cannabidiol (CBD), the major non-psychoactive component of cannabis, exhibits anti-inflammatory properties, but less is known about the immunomodulatory potential of CBD on activated natural killer (NK) cells and/or their targets. Many tumor cells present heat shock protein 70 (Hsp70) on their cell surface in a tumor-specific manner and although a membrane Hsp70 (mHsp70) positive phenotype serves as a target for Hsp70-activated NK cells, a high mHsp70 expression is associated with tumor aggressiveness. This study investigated the immuno-modulatory potential of CBD on NK cells stimulated with TKD Hsp70 peptide and IL-2 (TKD+IL-2) and also on HCT116 p53wt and HCT116 p53-/- colorectal cancer cells exhibiting high and low basal levels of mHsp70 expression. RESULTS: Apart from an increase in the density of NTB-A and a reduced expression of LAMP-1, the expression of all other activatory NK cell receptors including NKp30, NKG2D and CD69 which are significantly up-regulated after stimulation with TKD+IL-2 remained unaffected after a co-treatment with CBD. However, the release of major pro-inflammatory cytokines by NK cells such as interferon-γ (IFN-γ) and the effector molecule granzyme B (GrzB) was significantly reduced upon CBD treatment. With respect to the tumor target cells, CBD significantly reduced the elevated expression of mHsp70 but had no effect on the low basal mHsp70 expression. Expression of other NK cell ligands such as MICA and MICB remained unaffected, and the NK cell ligands ULBP and B7-H6 were not expressed on these target cells. Consistent with the reduced mHsp70 expression, treatment of both effector and target cells with CBD reduced the killing of high mHsp70 expressing tumor cells by TKD+IL-2+CBD pre-treated NK cells but had no effect on the killing of low mHsp70 expressing tumor cells. Concomitantly, CBD treatment reduced the TKD+IL-2 induced increased release of IFN-γ, IL-4, TNF-α and GrzB, but CBD had no effect on the release of IFN-α when NK cells were co-incubated with tumor target cells. CONCLUSION: Cannabidiol (CBD) may potentially diminish the anti-tumor effectiveness of TKD+IL-2 activated natural killer (NK) cells.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Cannabidiol (cbd) ; Cell Death ; Hsp70 Peptide Tkd ; Il-2 ; Natural Killer (nk) Cells ; Tp53; Natural-killer-cell; Heat-shock Proteins; P-glycoprotein; Plasma-membrane; Dendritic Cells; Nkg2d Receptor; T-cells; Hla-e; Heat-shock-protein-70; Hsp70
Sprache englisch
Veröffentlichungsjahr 2024
HGF-Berichtsjahr 2024
ISSN (print) / ISBN 0161-5890
e-ISSN 1872-9142
Zeitschrift Molecular Immunology
Quellenangaben Band: 174 Heft: , Seiten: , Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort The Boulevard, Langford Lane, Kidlington, Oxford Ox5 1gb, England
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Biological and Medical Imaging (IBMI)
POF Topic(s) 30205 - Bioengineering and Digital Health
Forschungsfeld(er) Enabling and Novel Technologies
PSP-Element(e) G-505500-001
Förderungen Bundesministerium fur Bildung und Forschung (BMBF)
DOI 10.1016/j.molimm.2024.07.008
WOS ID 001294022100001
Scopus ID 85200636933
PubMed ID 39126837
Erfassungsdatum 2024-09-30
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