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Original Article | Open Access

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

Shuangcheng Li1,2, Tianci Wang1,2, Xinghui Xiao1,2, Xiaodong Zheng1,2, Haoyu Sun1,2, Rui Sun1,2, Hongdi Ma1,2, Zhigang Tian1,2,3,4,5 ( ), Xiaohu Zheng1,2,5 ( )
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 Study, Chinese Academy of Medical Sciences, Beijing 100864, China
Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
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Abstract

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.

Keywords

phosphatidylserineimmune checkpointNK cellCD300Ahematologic malignancy

Electronic Supplementary Material

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Cancer Biology & Medicine
Volume 21 Issue 4,
April 2024
Pages 331-346
DOI: 10.20892/j.issn.2095-3941.2023.0341
Cite this article:
Li S, Wang T, Xiao X, et al. Blockade of CD300A enhances the ability of human NK cells to lyse hematologic malignancies. Cancer Biology & Medicine, 2024, 21(4): 331-346. https://doi.org/10.20892/j.issn.2095-3941.2023.0341

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Received: 08 October 2023
Accepted: 11 December 2023
Published: 29 February 2024
©2024 The Authors.

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