Targeting NKG2D/NKG2DL axis in multiple myeloma therapy

IF 9.3 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Cytokine & Growth Factor Reviews Pub Date : 2024-02-15 DOI:10.1016/j.cytogfr.2024.02.001

Zhaoyun Liu , Hao Wang , Hui Liu , Kai Ding , Hongli Shen , Xianghong Zhao , Rong Fu

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Abstract

Immune effector cells in patients with multiple myeloma (MM) are at the forefront of many immunotherapy treatments, and several methods have been developed to fully utilise the antitumour potential of immune cells. T and NK cell-derived immune lymphocytes both expressed activating NK receptor group 2 member D(NKG2D). This receptor can identify eight distinct NKG2D ligands (NKG2DL), including major histocompatibility complex class I (MHC) chain-related protein A and B (MICA and MICB). Their binding to NKG2D triggers effector roles in T and NK cells. NKG2DL is polymorphic in MM cells. The decreased expression of NKG2DL on the cell surface is explained by multiple mechanisms of tumour immune escape. In this review, we discuss the mechanisms by which the NKG2D/NKG2DL axis regulates immune effector cells and strategies for promoting NKG2DL expression and inhibiting its release in multiple myeloma and propose therapeutic strategies that increase the expression of NKG2DL in MM cells while enhancing the activation and killing function of NK cells.

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靶向 NKG2D/NKG2DL 轴治疗多发性骨髓瘤

多发性骨髓瘤（MM）患者的免疫效应细胞是许多免疫疗法的前沿，目前已开发出多种方法来充分利用免疫细胞的抗肿瘤潜力。T细胞和NK细胞衍生的免疫淋巴细胞都表达活化的NK受体2组D（NKG2D）。该受体可识别八种不同的 NKG2D 配体（NKG2DL），包括主要组织相容性复合体 I 类（MHC）链相关蛋白 A 和 B（MICA 和 MICB）。它们与 NKG2D 的结合会触发 T 细胞和 NK 细胞的效应作用。NKG2DL 在 MM 细胞中呈多态性。NKG2DL在细胞表面表达的减少可以用多种肿瘤免疫逃逸机制来解释。在这篇综述中，我们讨论了NKG2D/NKG2DL轴调节免疫效应细胞的机制，以及促进NKG2DL表达和抑制其在多发性骨髓瘤中释放的策略，并提出了增加NKG2DL在MM细胞中的表达，同时增强NK细胞活化和杀伤功能的治疗策略。

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来源期刊

Cytokine & Growth Factor Reviews 生物-生化与分子生物学

CiteScore

21.10

自引率

1.50%

发文量

审稿时长

22 days

期刊介绍： Cytokine & Growth Factor Reviews is a leading publication that focuses on the dynamic fields of growth factor and cytokine research. Our journal offers a platform for authors to disseminate thought-provoking articles such as critical reviews, state-of-the-art reviews, letters to the editor, and meeting reviews. We aim to cover important breakthroughs in these rapidly evolving areas, providing valuable insights into the multidisciplinary significance of cytokines and growth factors. Our journal spans various domains including signal transduction, cell growth and differentiation, embryonic development, immunology, tumorigenesis, and clinical medicine. By publishing cutting-edge research and analysis, we aim to influence the way researchers and experts perceive and understand growth factors and cytokines. We encourage novel expressions of ideas and innovative approaches to organizing content, fostering a stimulating environment for knowledge exchange and scientific advancement.

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