Expanded clinical-grade NK cells exhibit stronger effects than primary NK cells against HCMV infection

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外文摘要：Cytomegalovirus(CMV)reactivation remains a common complication and leads to high mortality in patients who undergo allogeneic hematopoietic stem cell transplantation(allo-HSCT).Early natural killer(NK)cell reconstitution may protect against the development of human CMV(HCMV)infection post-HSCT.Our previous data showed that ex vivo mbIL21/4-1BBL-expanded NK cells exhibited high cytotoxicity against leukemia cells.Nevertheless,whether expanded NK cells have stronger anti-HCMV function is unknown.Herein,we compared the anti-HCMV functions of ex vivo expanded NK cells and primary NK cells.Expanded NK cells showed higher expression of activating receptors,chemokine receptors and adhesion molecules;stronger cytotoxicity against HCMV-infected fibroblasts;and better inhibition of HCMV propagation in vitro than primary NK cells.In HCMV-infected humanized mice,expanded NK cell infusion resulted in higher NK cell persistence and more effective tissue HCMV elimination than primary NK cell infusion.A clinical cohort of 20 post-HSCT patients who underwent adoptive NK cell infusion had a significantly lower cumulative incidence of HCMV infection(HR=0.54,95%CI=0.32-0.93,p=0.042)and refractory HCMV infection(HR=0.34,95%CI=0.18-0.65,p=0.009)than controls and better NK cell reconstitution on day 30 post NK cell infusion.In conclusion,expanded NK cells exhibit stronger effects than primary NK cells against HCMV infection both in vivo and in vitro.

外文关键词：

Allogeneic haematopoietic stem cell transplantationNatural killer cellsHuman cytomegalovirus infectionAdoptive infusion

作者：

Qian-Nan Shang、Xing-Xing Yu、Zheng-Li Xu、Yu-Hong Chen、Ting-Ting Han、Yuan-Yuan Zhang、Meng Lv、Yu-Qian Sun、Yu Wang、Lan-Ping Xu、Xiao-Hui Zhang、Xiang-Yu Zhao、Xiao-Jun Huang

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作者单位：

Peking University People's Hospital,Peking University Institute of Hematology,National Clinical Research Center for Hematologic Disease,Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation,Peking University,Beijing,China

Peking-Tsinghua Center for Life Sciences,Academy for Advanced Interdisciplinary Studies,Peking University,Beijing,China

基金：

National Key Research and Development Program of ChinaMajor of the National Natural Science Foundation of ChinaKey Program of the National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaPeking University People's Hospital Research and Development FundsPeking University People's Hospital Research and Development Funds

项目编号：

2022YFA1103300822936308193000481870140820701848227022881370666RDX2019-14RDL2021-01

出版年：

2023

DOI：

10.1038/s41423-023-01046-5

中国免疫学杂志(英文版)

中国免疫学会

中国免疫学杂志(英文版)

CSTPCDCSCDSCI

影响因子：0.731

ISSN：1672-7681

年,卷(期)：2023.20(8)

参考文献量48