Hasim et al. showed that immune cells from PD-1 KO mice can, both in vitro and in vivo, acquire surface PD-1 (and other membrane proteins) through contact with PD-1+ tumor cells. Such surface acquisition by cells of membrane parts of other cells (known as trogocytosis) was SLAM receptor-dependent; neither PD-L1 nor Fc receptors were involved. Experiments with PD1+ and PD1- versions of a tumor susceptible to NK-mediated control indicated that trogocytosed PD-1 inhibits NK cell antitumor activity. PD-1 and tumor markers were observed on NK cells in patient samples, suggesting clinical relevance of trogocytosis.
Contributed by Margot O’Toole
ABSTRACT: Trogocytosis modulates immune responses, with still unclear underlying molecular mechanisms. Using leukemia mouse models, we found that lymphocytes perform trogocytosis at high rates with tumor cells. While performing trogocytosis, both Natural Killer (NK) and CD8(+) T cells acquire the checkpoint receptor PD-1 from leukemia cells. In vitro and in vivo investigation revealed that PD-1 on the surface of NK cells, rather than being endogenously expressed, was derived entirely from leukemia cells in a SLAM receptor-dependent fashion. PD-1 acquired via trogocytosis actively suppressed NK cell antitumor immunity. PD-1 trogocytosis was corroborated in patients with clonal plasma cell disorders, where NK cells that stained for PD-1 also stained for tumor cell markers. Our results, in addition to shedding light on a previously unappreciated mechanism underlying the presence of PD-1 on NK and cytotoxic T cells, reveal the immunoregulatory effect of membrane transfer occurring when immune cells contact tumor cells.