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.
When killers become thieves: Trogocytosed PD-1 inhibits NK cells in cancer / Hasim, M. S.; Marotel, M.; Hodgins, J. J.; Vulpis, E.; Makinson, O. J.; Asif, S.; Shih, H. -Y.; Scheer, A. K.; Macmillan, O.; Alonso, F. G.; Burke, K. P.; Cook, D. P.; Li, R.; Petrucci, M. T.; Santoni, A.; Fallon, P. G.; Sharpe, A. H.; Sciume, G.; Veillette, A.; Zingoni, A.; Gray, D. A.; Mccurdy, A.; Ardolino, M.. - In: SCIENCE ADVANCES. - ISSN 2375-2548. - 8:15(2022). [10.1126/sciadv.abj3286]
When killers become thieves: Trogocytosed PD-1 inhibits NK cells in cancer
Vulpis E.Methodology
;Petrucci M. T.;Sciume G.;Zingoni A.Formal Analysis
;Ardolino M.
2022
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
