细胞毒性T细胞
生物
免疫系统
白血病
NK-92
白细胞介素21
细胞生物学
Janus激酶3
CD8型
癌症研究
过继性细胞移植
癌细胞
免疫学
体外
癌症
T细胞
生物化学
遗传学
作者
Mohamed Shaad Hasim,Marie Marotel,Jonathan J. Hodgins,Elisabetta Vulpis,Olivia J Makinson,Sara Asif,Han-Yu Shih,Amit Scheer,Olivia MacMillan,Fernando García Alonso,Kelly P. Burke,David P. Cook,Rui Li,Maria Teresa Petrucci,Angela Santoni,Padraic G. Fallon,Arlene H. Sharpe,Giuseppe Sciumè,André Veillette,Alessandra Zingoni,Douglas A. Gray,Arleigh McCurdy,Michele Ardolino
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2022-04-15
卷期号:8 (15)
被引量:46
标识
DOI:10.1126/sciadv.abj3286
摘要
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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