OncoImmunology (Mar 2019)

PD-1 in human NK cells: evidence of cytoplasmic mRNA and protein expression

  • Francesca R. Mariotti,
  • Stefania Petrini,
  • Tiziano Ingegnere,
  • Nicola Tumino,
  • Francesca Besi,
  • Francesca Scordamaglia,
  • Enrico Munari,
  • Silvia Pesce,
  • Emanuela Marcenaro,
  • Alessandro Moretta,
  • Paola Vacca,
  • Lorenzo Moretta

DOI
https://doi.org/10.1080/2162402X.2018.1557030
Journal volume & issue
Vol. 8, no. 3

Abstract

Read online

Under physiological conditions, PD-1/PD-L1 interactions regulate unwanted over-reactions of immune cells and contribute to maintain peripheral tolerance. However, in tumor microenvironment, this interaction may greatly compromise the immune-mediated anti-tumor activity. PD-1+ NK cells have been detected in high percentage in peripheral blood and ascitic fluid of ovarian carcinoma patients. To acquire information on PD-1 expression and physiology in human NK cells, we analyzed whether PD-1 mRNA and protein are present in resting, surface PD-1−, NK cells from healthy donors. Both different splicing isoforms of PD-1 mRNA and a cytoplasmic pool of PD-1 protein were detected. Similar results were obtained also from both in vitro-activated and tumor-associated NK cells. PD-1 mRNA and protein were higher in CD56dim than in CD56bright NK cells. Confocal microscopy analyses revealed that PD-1 protein is present in virtually all NK cells analyzed. The present findings are compatible with a rapid surface expression of PD-1 in NK cells in response to appropriate, still undefined, stimuli.

Keywords