@Article{ecn.2019.0440,
AUTHOR = {Katarina Mirjačić Martinović, Milica Milićević, Annette K Larsen, Radan Džodić, Vladimir Jurišić, Gordana Konjević, Ana Vuletić},
TITLE = {Effect of cytokines on NK cell activity and activating receptor expression in high-risk cutaneous melanoma patients},
JOURNAL = {European Cytokine Network},
VOLUME = {30},
YEAR = {2019},
NUMBER = {4},
PAGES = {160--167},
URL = {http://www.techscience.com/ECN/v30n4/65387},
ISSN = {1952-4005},
ABSTRACT = {Objective: Stage II melanoma patients have high risk for regional and distant metastases and may benefit
from novel therapeutic strategies. To clarify the role of NK cells in Stage II melanoma, we characterized the cytotoxic
activity of NK cells and the expression of various activating and inhibitory receptors in high-risk cutaneous melanoma
patients (Stages IIB and IIC) compared to low-risk patients (Stage IA). Materials and Methods: Native and cytokinetreated
peripheral blood mononuclear cells were used for functional and phenotypical analyses. Results: Compared to
Stage IA-B patients, Stage IIB-C patients showed significantly decreased NK cell activity, as well as decreased
expression of the activating NKG2D and CD161 receptors, most likely due to increased serum levels of the
immunosuppressive cytokine TGF-β1 in these patients. Interestingly, treatment of periperal blood mononuclear cells
with IFN-α, IL-2, IL-12 or the combination of IL-12 and IL-18 significantly induced NK cell activity for both groups of
melanoma patients. However, only low-risk patients had a significant increase in the expression of the NKG2D receptor
after in vitro treatment with IFN-α, as well as an significant increase in the expression of CD161 after treatment with
IFN-α or IL-12. Although IL-2 induced the expression of NKG2D in both groups of patients, this increase was
significantly lower in high-risk melanoma. Conclusion: NK cell parameters may be useful as biomarkers of disease
progression in localized melanoma patients. Our results further suggest that the use of NK cell-activating cytokines in
combination with inhibitors of immunosuppressive factors like TGF-β1 could be a therapeutic option for the treatment
of high-risk cutaneous melanoma patients.},
DOI = {10.1684/ecn.2019.0440}
}