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

Growth Factors. 2022 Nov;40(5-6):231-239. doi: 10.1080/08977194.2022.2124915. Epub 2022 Sep 21.

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.

Keywords: CD107a; NK cells; NKG2D; NKp46; TGF-β1; metastatic melanoma patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Killer Cells, Natural
  • Leukocytes, Mononuclear / metabolism
  • Leukocytes, Mononuclear / pathology
  • Melanoma* / metabolism
  • Melanoma* / pathology
  • NK Cell Lectin-Like Receptor Subfamily K* / genetics
  • NK Cell Lectin-Like Receptor Subfamily K* / metabolism
  • Transforming Growth Factor beta1* / genetics

Substances

  • NK Cell Lectin-Like Receptor Subfamily K
  • Transforming Growth Factor beta1
  • TGFB1 protein, human