Platelet factor 4 regulates T cell effector functions in malignant pleural effusions

Cancer Lett. 2020 Oct 28:491:78-86. doi: 10.1016/j.canlet.2020.06.014. Epub 2020 Jul 26.

Abstract

Malignant pleural effusion (MPE) is defined as the presence of tumor cells in pleural fluid and it is a fatal complication of advanced lung adenocarcinoma (LAC). To understand the immune response to the tumor in MPE, we compared the concentration of immunomodulatory factors in MPE of LAC and pleural effusion of heart failure (HF) patients by ELISA, and the proliferation and cytotoxic phenotype of T cells stimulated in the presence of LAC and HF pleural fluids by cytometry. Platelet factor 4 (PF4), vascular endothelial growth factor (VEGF), transforming growth factor beta (TGF-β) and P-selectin levels were higher in LAC than in HF pleural fluids. However, plasmatic PF4 and P-selectin levels were similar in LAC and HF. VEGF positively correlated with TGF-β and sPD-L1 in LAC but not in HF pleural fluids. LAC pleural fluids also inhibited T lymphocyte proliferation and cytotoxicity and reduced IL-17 production. PF4 levels inversely correlated with T cell function. The high content of PF4 in MPE was associated with poor prognosis. Our findings suggest that an impaired response of T lymphocytes induced by PF4 provides a significant advantage for tumor progression.

Keywords: Immunosuppression; Lung cancer; MPE; PF4; Platelet-derived soluble factors; T lymphocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma of Lung / complications*
  • Adenocarcinoma of Lung / mortality
  • Aged
  • Aged, 80 and over
  • Female
  • Heart Failure / immunology
  • Humans
  • Lung Neoplasms / complications*
  • Lung Neoplasms / mortality
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Platelet Factor 4 / analysis
  • Platelet Factor 4 / physiology*
  • Pleural Effusion, Malignant / immunology*
  • Pleural Effusion, Malignant / mortality
  • T-Lymphocytes / immunology*
  • Transforming Growth Factor beta / analysis
  • Vascular Endothelial Growth Factor A / analysis

Substances

  • Transforming Growth Factor beta
  • Vascular Endothelial Growth Factor A
  • Platelet Factor 4