Decreased expression of NKG2D, NKp46, DNAM-1 receptors, and intracellular perforin and STAT-1 effector molecules in NK cells and their dim and bright subsets in metastatic melanoma patients
2014
Аутори:
Martinovic, Katarina M. MirjacicBabovic, Nada Lj.
Džodić, Radan R.
Jurisic, Vladimir B.
Tanić, Nikola
Konjevic, Gordana M.
Тип документа:
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт:
Although natural killer (NK) cells play an important antitumor role,
melanoma cells may affect their effector functions. In this study, we
analyzed the expression of various receptors and effector molecules in
NK cells and their subsets in metastatic melanoma (MM) patients compared
with healthy controls (HCs). In HC and MM patients, we analyzed NK cell
activity using a chromium release assay and the expression of CD107a
degranulation marker, activating NKG2D, NKp46, DNAM-1, and inhibitory
CD158a and CD158b receptors, IL-12R beta 1, IL-12R beta 2, intracellular
interferon (IFN)-gamma, perforin, and STAT-1 in CD3-CD56 + NK cells, and
cytotoxic CD3-CD56 dim and immunoregulatory CD3-CD56 bright subsets by
flow cytometry. MM patients compared with HC not only had significantly
decreased NK cell activity, lower expression of CD107a, and impaired
IFN-gamma production but also had decreased expression of activating
NKG2D, NKp46, and DNAM-1 receptors, which was followed by lower
expression of perforin, STAT-1, and both IL-12R subunits in NK cells. In
MM patients only, there was a positive correlation between NKG2D
expression and degranulation capacity, as well as IFN-gamma production
in NK cells. Analysis of the expression of various parameters of NK cell
effector functions between MM patients with different localization of
distant metastases showed that patients in the unfavorable M1c subclass
had decreased expression of NKG2D and NKp46 on NK cells compared with
patients in the M1a + b group. Downregulated NKG2D, NKp46, and DNAM-1
receptors associated with impaired NK cell effector function are
important biomarkers of advanced disease with a poor prognosis in
melanoma patients. (C) 2014 Wolters Kluwer Health vertical bar
Lippincott Williams \& Wilkins.
Кључне речи:
cytotoxicity; interferon-gamma production; metastatic melanoma; natural killer cells; perforinИзвор:
Melanoma Research, 2014, 24, 4, 295-304
DOI: 10.1097/CMR.0000000000000072
ISSN: 1473-5636