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

Cancer Biology & Medicine 2024年第4期21卷 331-346页

作者： Shuangcheng Li Tianci Wang Xinghui Xiao Xiaodong Zheng Haoyu Sun Rui Sun Hongdi Ma Zhigang Tian Xiaohu Zheng hefei National Research Center for Physical Sciences at Microscale The CAS Key Laboratory of Innate Immunity and Chronic DiseaseSchool of Basic Medical SciencesCenter for Advanced Interdisciplinary Science and Biomedicine of IHMDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230027China Institute of Immunology University of Science and Technology of ChinaHefei 230027China hefei tg immunopharma corporation limited Hefei 230601China Research Unit of NK Cell Study Chinese Academy of Medical SciencesBeijing 100864China Key Laboratory of Quantitative Synthetic Biology Shenzhen Institute of Synthetic BiologyShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China

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 ***: 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 ***: 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

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The use of supercytokines, immunocytokines, engager cytokines, and other synthetic cytokines in immunotherapy

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Cellular & Molecular Immunology 2022年第2期19卷 192-209页

作者： Xiaohu Zheng Yaqi Wu Jiacheng Bi Yingying Huang Ying Cheng Yangyang Li Yuwei Wu Guoshuai Cao Zhigang Tian CAS Key Laboratory of Quantitative Engineering Biology Shenzhen Institute of Synthetic BiologyShenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhenChina Shenzhen Institute of Synthetic Biology Shenzhen Institute of Advanced TechnologyChinese Academy of Sciences518055ShenzhenChina hefei National Laboratory for Physical Sciences at Microscale CAS Key Laboratory of Innate Immunity and Chronic DiseaseSchool of Basic Medical SciencesDivision of Life Sciences and MedicineUniversity of Science and Technology of China230027HefeiChina hefei tg immunopharma corporation limited HefeiChina

Cytokines exert powerful immunomodulatory effects that are critical to physiology and pathology in *** application of natural cytokines in clinical studies has not been clearly established,and there are often problems associated with toxicity or lack of *** key reasons can be attributed to the pleiotropy of cytokine receptors and undesired activation of off-target *** a deeper understanding of the structural principles and functional signals of cytokine-receptor interactions,artificial modification of cytokine signaling through protein engineering and synthetic immunology has become an increasingly feasible and powerful *** cytokines are designed to selectively target ***,the theoretical and experimental evidence of cytokine engineering is reviewed,and the“supercytokines”resulting from structural enhancement and the“immunocytokines”generated by antibody fusion are ***,the“engager cytokines”formed by the crosslinking of cytokines and bispecific immune engagers and other synthetic cytokines formed by nonnatural analogs are also discussed.

关键词： Supercytokines immunocytokines engager cytokines synthetic cytokines immunotherapy

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