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

Authors :
Carlos Zamora
Nuria Calvo
Maria Mulet
José M. Porcel
Virginia Pajares
Ana M. Muñoz-Fernandez
Silvia Vidal
Juan C. Nieto
Aureli Esquerda
Source :
CANCER LETTERS, r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau, instname, r-IIB SANT PAU: Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau, Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Publication Year :
2020
Publisher :
Elsevier BV, 2020.

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-beta) 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-beta 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.

Details

ISSN :
03043835
Volume :
491
Database :
OpenAIRE
Journal :
Cancer Letters
Accession number :
edsair.doi.dedup.....2e60f785f6dc5ac60e8cfc8b55441565
Full Text :
https://doi.org/10.1016/j.canlet.2020.06.014