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

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

机构地区：[1]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 [2]Institute of Immunology,University of Science and Technology of China,Hefei 230027,China [3]Hefei TG ImmunoPharma Corporation Limited,Hefei 230601,China [4]Research Unit of NK Cell Study,Chinese Academy of Medical Sciences,Beijing 100864,China [5]Key Laboratory of Quantitative Synthetic Biology,Shenzhen Institute of Synthetic Biology,Shenzhen Institute of Advanced Technology,Chinese Academy of Sciences,Shenzhen 518055,China

出　　处：《Cancer Biology & Medicine》2024年第4期331-346,共16页癌症生物学与医学（英文版）

基　　金：supported by the National Key R&D Program of China (2019YFA0508502/3 and 2021YFC2300604);the Natural Science Foundation of China (Reference numbers 82388201, 82241216, and 32270963);the Research Funds of Center for Advanced Interdisciplinary Science and Biomedicine of IHM (QYZD20220008);the Anhui Key Research and Development Plan (Reference number 2023z04020011)。

摘　　要：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.

关 键 词：NK cell CD300A PHOSPHATIDYLSERINE immune checkpoint hematologic malignancy 

分 类 号：R733[医药卫生—肿瘤]