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Publication : When killers become thieves: Trogocytosed PD-1 inhibits NK cells in cancer.

First Author  Hasim MS Year  2022
Journal  Sci Adv Volume  8
Issue  15 Pages  eabj3286
PubMed ID  35417234 Mgi Jnum  J:327496
Mgi Id  MGI:7263988 Doi  10.1126/sciadv.abj3286
Citation  Hasim MS, et al. (2022) When killers become thieves: Trogocytosed PD-1 inhibits NK cells in cancer. Sci Adv 8(15):eabj3286
abstractText  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.
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