Abstract
NK cells are key effectors of cancer immunosurveillance and immunotherapy and yet, much is still unknown about how cancer evades NK cell responses. Recent studies showed that checkpoint receptors, including PD-1, inhibit NK cell functions, but the mechanisms underlying the expression of these receptors remains unknown. Here, using two mouse models of leukemia, we show that NK cells, rather than intrinsically expressing the protein, are decorated with exogenous PD-1 by acquisition of membrane fragments from tumor cells. PD-1 acquisition, both ex vivo and in vivo, was a feature not only of NK cells, but also of CD8+ T cells. PD-1 acquisition occurred with a mechanism consistent with trogocytosis and did not require engagement of PD-1-ligands on NK cells. In vivo results were corroborated in humans, where PD-1+ NK cells from multiple myeloma patients also stained for cancer cell markers. Our results, in addition to shedding light on a previously unappreciated mechanism underlying the presence of PD-1 on NK and T cells, reveal the immuno-regulatory effect of membrane transfer occurring when immune cells contact tumor cells.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
The authors have declared that no conflict of interest exists.