NK cell-based immunotherapy strategies for myeloid leukemia

Myeloid leukemia (ML) is a clonal malignant disease with abnormal hematopoietic stem cells. With the emergence of novel immunotherapies, such as CAR-T, therapeutic outcomes in ML patients have improved, while significant challenges persist, including severe adverse events and disease recurrence. Nat...

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Main Authors: Lin Zhang, Yibo Zhao, Yan Dong, Xiuxing Jiang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1621885/full
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author Lin Zhang
Yibo Zhao
Yan Dong
Xiuxing Jiang
author_facet Lin Zhang
Yibo Zhao
Yan Dong
Xiuxing Jiang
author_sort Lin Zhang
collection DOAJ
description Myeloid leukemia (ML) is a clonal malignant disease with abnormal hematopoietic stem cells. With the emergence of novel immunotherapies, such as CAR-T, therapeutic outcomes in ML patients have improved, while significant challenges persist, including severe adverse events and disease recurrence. Natural killer cells (NK cells) are “natural killers” of the immune system that do not require antigen presentation and responsible for recognizing and destroying tumor cells. Some NK cells-based clinical experiments have been carried out and achieved remarkable results with lower side effects in ML. Crucially, within the ML microenvironment, NK cells frequently exhibit more severe functional exhaustion compared with T cells, characterized by impaired cytotoxicity, cytokine production, and proliferative capacity which limits anti-ML efficacy of NK cells. However, clinical studies utilizing NK cell-based therapies (e.g., adoptive transfer, CAR-NK cells) have demonstrated promising results with favorable safety profiles, underscoring their therapeutic potential. Therefore, developing more strategies based on NK cell is of great clinical significance for the treatment of ML. In this review, we systematically analysed the relationship between ML and NK cells, aiming to propose more novel protocols for NK cell expansion and persistence enhancement, establish evidence-based guidelines for next-generation NK cell-based immunotherapies in ML treatment.
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spelling doaj-art-11340900cd4d4f26ac2fc20e37ebaca12025-08-20T03:17:54ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-07-011610.3389/fimmu.2025.16218851621885NK cell-based immunotherapy strategies for myeloid leukemiaLin Zhang0Yibo Zhao1Yan Dong2Xiuxing Jiang3Department of Pharmacy, Daping Hospital, Army Medical University, Chongqing, ChinaDepartment of Pharmacy, Daping Hospital, Army Medical University, Chongqing, ChinaDepartment of Oncology, Southwest Hospital, Army Medical University, Chongqing, ChinaFrontier Medical Training Brigade, Army Medical University, Xinjiang, ChinaMyeloid leukemia (ML) is a clonal malignant disease with abnormal hematopoietic stem cells. With the emergence of novel immunotherapies, such as CAR-T, therapeutic outcomes in ML patients have improved, while significant challenges persist, including severe adverse events and disease recurrence. Natural killer cells (NK cells) are “natural killers” of the immune system that do not require antigen presentation and responsible for recognizing and destroying tumor cells. Some NK cells-based clinical experiments have been carried out and achieved remarkable results with lower side effects in ML. Crucially, within the ML microenvironment, NK cells frequently exhibit more severe functional exhaustion compared with T cells, characterized by impaired cytotoxicity, cytokine production, and proliferative capacity which limits anti-ML efficacy of NK cells. However, clinical studies utilizing NK cell-based therapies (e.g., adoptive transfer, CAR-NK cells) have demonstrated promising results with favorable safety profiles, underscoring their therapeutic potential. Therefore, developing more strategies based on NK cell is of great clinical significance for the treatment of ML. In this review, we systematically analysed the relationship between ML and NK cells, aiming to propose more novel protocols for NK cell expansion and persistence enhancement, establish evidence-based guidelines for next-generation NK cell-based immunotherapies in ML treatment.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1621885/fullmyeloid leukemiaNK cellexhaustiontherapeutic potentialimmunobiology
spellingShingle Lin Zhang
Yibo Zhao
Yan Dong
Xiuxing Jiang
NK cell-based immunotherapy strategies for myeloid leukemia
Frontiers in Immunology
myeloid leukemia
NK cell
exhaustion
therapeutic potential
immunobiology
title NK cell-based immunotherapy strategies for myeloid leukemia
title_full NK cell-based immunotherapy strategies for myeloid leukemia
title_fullStr NK cell-based immunotherapy strategies for myeloid leukemia
title_full_unstemmed NK cell-based immunotherapy strategies for myeloid leukemia
title_short NK cell-based immunotherapy strategies for myeloid leukemia
title_sort nk cell based immunotherapy strategies for myeloid leukemia
topic myeloid leukemia
NK cell
exhaustion
therapeutic potential
immunobiology
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1621885/full
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AT yibozhao nkcellbasedimmunotherapystrategiesformyeloidleukemia
AT yandong nkcellbasedimmunotherapystrategiesformyeloidleukemia
AT xiuxingjiang nkcellbasedimmunotherapystrategiesformyeloidleukemia