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

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)1557030
Issue number3
Publication statusPublished - Dec 25 2019


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