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从天然防御者到治疗勇士:HIV免疫疗法中的自然杀伤细胞

From natural defenders to therapeutic warriors: NK cells in HIV immunotherapy.

作者信息

Laeremans Thessa, Janssens Amber, Aerts Joeri L

机构信息

Neuro-Aging and Viro-Immunotherapy (NAVI) Research Group, Faculty of Pharmacy, Vrije Universiteit Brussel (VUB), Brussels, Belgium.

出版信息

Immunotherapy. 2025 Feb;17(2):133-145. doi: 10.1080/1750743X.2025.2460965. Epub 2025 Feb 5.


DOI:10.1080/1750743X.2025.2460965
PMID:39905963
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11901454/
Abstract

Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells both play essential roles in controlling viral infections by eliminating virus-infected cells. Unlike CTLs, which require priming and activation by antigen-presenting cells, NK cells possess a remarkable capacity to mount a rapid antiviral immune response immediately after infection. Additionally, they can bolster the adaptive immune system by secreting cytokines and directly interacting with other immune cells. However, during chronic human immunodeficiency virus (HIV) infection, various immune cells, including NK cells, experience functional impairments. This has led to the exploration of NK cell-based immunotherapy as a promising strategy to reverse these dysfunctions and contribute to the pursuit of a functional cure for HIV. Building on the success of NK cell therapies in cancer treatment, these approaches offer significant potential for transforming the HIV cure field. This review provides a comprehensive overview of the latest advances in NK cell-based immunotherapy for HIV, outlining the progress made and the key challenges that must be overcome to achieve a functional cure for people living with HIV.

摘要

细胞毒性T淋巴细胞(CTL)和自然杀伤(NK)细胞在通过清除病毒感染细胞来控制病毒感染方面都发挥着重要作用。与需要抗原呈递细胞启动和激活的CTL不同,NK细胞具有在感染后立即迅速发起抗病毒免疫反应的显著能力。此外,它们可以通过分泌细胞因子并直接与其他免疫细胞相互作用来增强适应性免疫系统。然而,在慢性人类免疫缺陷病毒(HIV)感染期间,包括NK细胞在内的各种免疫细胞都会出现功能障碍。这促使人们探索基于NK细胞的免疫疗法,将其作为一种有前景的策略来逆转这些功能障碍,并为实现HIV的功能性治愈做出贡献。基于NK细胞疗法在癌症治疗中的成功,这些方法为变革HIV治愈领域提供了巨大潜力。本综述全面概述了基于NK细胞的HIV免疫疗法的最新进展,概述了所取得的进展以及为实现HIV感染者的功能性治愈必须克服的关键挑战。

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本文引用的文献

[1]
CRISPR/Cas9 editing of NKG2A improves the efficacy of primary CD33-directed chimeric antigen receptor natural killer cells.

Nat Commun. 2024-9-30

[2]
Functional comparison of Fc-engineering strategies to improve anti-HIV-1 antibody effector functions.

Antiviral Res. 2024-11

[3]
NKG2C and NKG2A coexpression defines a highly functional antiviral NK population in spontaneous HIV control.

JCI Insight. 2024-9-17

[4]
Dual blockade of IL-10 and PD-1 leads to control of SIV viral rebound following analytical treatment interruption.

Nat Immunol. 2024-10

[5]
Afucosylated broadly neutralizing antibodies enhance clearance of HIV-1 infected cells through cell-mediated killing.

Commun Biol. 2024-8-9

[6]
High-dimensional single-cell analysis of human natural killer cell heterogeneity.

Nat Immunol. 2024-8

[7]
Natural killer cell therapies.

Nature. 2024-2

[8]
Bispecific antibodies promote natural killer cell-mediated elimination of HIV-1 reservoir cells.

Nat Immunol. 2024-3

[9]
Safety and Virologic Impact of Haploidentical NK Cells Plus Interleukin 2 or N-803 in HIV Infection.

J Infect Dis. 2024-5-15

[10]
scMD facilitates cell type deconvolution using single-cell DNA methylation references.

Commun Biol. 2024-1-2

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