Decreased expression of pSTAT, IRF-1 and DAP10 signalling molecules in peripheral blood lymphocytes of patients with metastatic melanoma.

摘要: Aims As numerous signalling molecules regulate effector functions of peripheral blood lymphocytes (PBLs) that have an important anti-tumour activity, the aim this study was to analyse their level in patients with metastatic melanoma (MM) compared healthy controls (HCs). Methods Peripheral mononuclear cells (PBMCs) 36 MMs and 28 HCs were analysed for perforin, interferon-regulating transcription factor-1 (IRF-1), DAP10 Src homology 2 domain-containing tyrosine phosphatase-1 by reverse transcriptase PCR, phosphorylated signal transducers activators (pSTAT)-1, pSTAT-4, pSTAT-5 western blot interferon (IFN)-γ production ELISA. The expression activating NKG2D inhibitory killer immunoglobulin-like receptors (KIR), CD158a CD158b, on PBL, CD3−CD56+ natural (NK) CD3+CD8+ cytotoxic T (CTLs), as well percentage CD14+HLA-DR- PBMC estimated flow cytometry. Results Patients MM, HCs, had significantly lower molecule perforin decreased IFN-γ production, pSTAT-1, IRF-1 PBMC. Furthermore, MM receptor PBL NK low its contrary no changes KIR all investigated cells. These results could be associated increased immunosuppressive CD14+HLA-DR− myeloid-derived suppressor detected MM. Conclusions altered represent biomarkers impaired immunoregulatory function these cells, indicating melanoma-associated immunosuppression facilitates tumour progression.