Increased circulating TGF-β1 is associated with impairment in NK cell effector functions in metastatic melanoma patients

Abstract

Transforming growth factor beta (TGF-β) plays a complex role in carcinogenesis. In 30 melanoma patients and 20 healthy controls (HC) we analysed functional and phenotypic characteristics of NK cells by Flow cytometry, gene expression of TGF-β1 in peripheral blood mononuclear cells by qPCR and serum and supernatant level of free TGF-β1 by ELISA. Melanoma patients had significantly higher serum level of circulatingTGF-β1 compared to HC, especially those with metastasis into the central nervous system (subclass M1d) and high LDH serum values. Melanoma patients compared to HC had significantly higher level of TGF-β1 gene in PBMC. TGF-β1 serum values negatively correlate with NK cell activity analysed by CD107a (degranulation marker), IFN-γ, NKG2D, and NKp46 in patients. Study shows the association of high level of TGF-β1 with NK cell inhibition in patients represents the main mechanism of tumour immune evasion. Targeting TGF-β may become an important cancer treatment for improving antitumor immunity.