Please use this identifier to cite or link to this item: https://scidar.kg.ac.rs/handle/123456789/11783
Title: Decreased expression of pSTAT, IRF-1 and DAP10 signalling molecules in peripheral blood lymphocytes of patients with metastatic melanoma
Authors: Mirjacic Martinović K.
Srdic-Rajic, Tatjana
Babovic N.
Dzodic, Radan
Jurisic, Vladimir
Konjević G.
Issue Date: 2016
Abstract: Aims: As numerous signalling molecules regulate effector functions of peripheral blood lymphocytes (PBLs) that have an important anti-tumour activity, the aim of this study was to analyse their level in patients with metastatic melanoma (MM) compared with healthy controls (HCs). Methods: Peripheral blood mononuclear cells (PBMCs) of 36 MMs and 28 HCs were analysed for the level of perforin, interferon-regulating transcription factor-1 (IRF-1), DAP10 and Src homology 2 domain-containing tyrosine phosphatase-1 by reverse transcriptase PCR, level of phosphorylated signal transducers and activators of transcription (pSTAT)-1, pSTAT-4, pSTAT-5 by western blot and interferon (IFN)-γ production by ELISA. The expression of activating NKG2D and inhibitory killer immunoglobulin-like receptors (KIR), CD158a and CD158b, on PBL, CD3-CD56+ natural killer (NK) cells and CD3+CD8+ cytotoxic T lymphocytes (CTLs), as well as the percentage of CD14+HLA-DR-cells in PBMC were estimated by flow cytometry. Results: Patients with MM, compared with HCs, had significantly lower level of cytotoxic molecule perforin and decreased IFN-γ production, as well as lower level of pSTAT-1, pSTAT-4, pSTAT-5 and IRF-1 signalling molecules in PBMC. Furthermore, MM had decreased expression of activating NKG2D receptor on PBL and NK cells and low level of its DAP10 signalling molecule contrary to no changes in KIR expression on all investigated cells. These results could be associated with increased percentage of immunosuppressive CD14+HLA-DR-myeloid-derived suppressor cells detected in patients with MM. Conclusions: The altered signalling molecules of PBL could represent biomarkers of impaired cytotoxic and immunoregulatory function of these cells, indicating melanoma-associated immunosuppression that facilitates tumour progression.
URI: https://scidar.kg.ac.rs/handle/123456789/11783
Type: article
DOI: 10.1136/jclinpath-2015-203107
ISSN: 0021-9746
SCOPUS: 2-s2.0-84961774954
Appears in Collections:Faculty of Medical Sciences, Kragujevac

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