首页|Blockade of CD300A enhances the ability of human NK cells to lyse hematologic malignancies

Blockade of CD300A enhances the ability of human NK cells to lyse hematologic malignancies

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Objective:The human cluster of differentiation(CD)300A,a type-Ⅰ transmembrane protein with immunoreceptor tyrosine-based inhibitory motifs,was investigated as a potential immune checkpoint for human natural killer(NK)cells targeting hematologic malignancies(HMs).Methods:We implemented a stimulation system involving the CD300A ligand,phosphatidylserine(PS),exposed to the outer surface of malignant cells.Additionally,we utilized CD300A overexpression,a CD300A blocking system,and a xenotransplantation model to evaluate the impact of CD300A on NK cell efficacy against HMs in in vitro and in vivo settings.Furthermore,we explored the association between CD300A and HM progression in patients.Results:Our findings indicated that PS hampers the function of NK cells.Increased CD300A expression inhibited HM lysis by NK cells.CD300A overexpression shortened the survival of HM-xenografted mice by impairing transplanted NK cells.Blocking PS-CD300A signals with antibodies significantly amplified the expression of lysis function-related proteins and effector cytokines in NK cells,thereby augmenting the ability to lyse HMs.Clinically,heightened CD300A expression correlated with shorter survival and an"exhausted"phenotype of intratumoral NK cells in patients with HMs or solid tumors.Conclusions:These results propose CD300A as a potential target for invigorating NK cell-based treatments against HMs.

NK cellCD300Aphosphatidylserineimmune checkpointhematologic malignancy

Shuangcheng Li、Tianci Wang、Xinghui Xiao、Xiaodong Zheng、Haoyu Sun、Rui Sun、Hongdi Ma、Zhigang Tian、Xiaohu Zheng

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Hefei National Research Center for Physical Sciences at Microscale,The CAS Key Laboratory of Innate Immunity and Chronic Disease,School of Basic Medical Sciences,Center for Advanced Interdisciplinary Science and Biomedicine of IHM,Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei 230027,China

Institute of Immunology,University of Science and Technology of China,Hefei 230027,China

Hefei TG ImmunoPharma Corporation Limited,Hefei 230601,China

Research Unit of NK Cell St

Key Laboratory of Quantitative Synthetic Biology,Shenzhen Institute of Synthetic Biology

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国家重点研发计划国家重点研发计划国家自然科学基金国家自然科学基金国家自然科学基金Research Funds of Center for Advanced Interdisciplinary Science and Biomedicine of IHMAnhui Key Research and Development Plan

2019YFA0508502/32021YFC2300604Reference numbers 823882018224121632270963QYZD20220008Reference number 2023z04020011

2024

10.20892/j.issn.2095-3941.2023.0341

癌症生物学与医学(英文版)
中国抗癌协会

癌症生物学与医学(英文版)

CSTPCD
影响因子：1.07
ISSN：2095-3941
年,卷(期)：2024.21(4)
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