Targeting natural killer cells: from basic biology to clinical application in hematologic malignancies.

IF 9.4 1区医学 Q1 HEMATOLOGY Experimental Hematology & Oncology Pub Date : 2024-02-23 DOI:10.1186/s40164-024-00481-y

Juanjuan Shang, Shunfeng Hu, Xin Wang

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Abstract

Natural killer (NK) cell belongs to innate lymphoid cell family that contributes to host immunosurveillance and defense without pre-immunization. Emerging studies have sought to understand the underlying mechanism behind NK cell dysfunction in tumor environments, and provide numerous novel therapeutic targets for tumor treatment. Strategies to enhance functional activities of NK cell have exhibited promising efficacy and favorable tolerance in clinical treatment of tumor patients, such as immune checkpoint blockade (ICB), chimeric antigen receptor NK (CAR-NK) cell, and bi/trispecific killer cell engager (BiKE/TriKE). Immunotherapy targeting NK cell provides remarkable advantages compared to T cell therapy, including a decreased rate of graft versus-host disease (GvHD) and neurotoxicity. Nevertheless, advanced details on how to support the maintenance and function of NK cell to obtain better response rate and longer duration still remain to be elucidated. This review systematically summarizes the profound role of NK cells in tumor development, highlights up-to-date advances and current challenges of therapy targeting NK cell in the clinical treatment of hematologic malignancies.

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靶向自然杀伤细胞：从基础生物学到血液恶性肿瘤的临床应用。

自然杀伤（NK）细胞属于先天性淋巴细胞家族，无需预先免疫即可参与宿主免疫监视和防御。新近的研究试图了解肿瘤环境中 NK 细胞功能失调背后的潜在机制，并为肿瘤治疗提供了许多新的治疗靶点。在肿瘤患者的临床治疗中，增强 NK 细胞功能活性的策略已显示出良好的疗效和耐受性，如免疫检查点阻断（ICB）、嵌合抗原受体 NK（CAR-NK）细胞和双/特异性杀伤细胞诱导体（BiKE/TriKE）。与T细胞疗法相比，以NK细胞为靶点的免疫疗法具有显著优势，包括降低移植物抗宿主疾病（GvHD）发生率和神经毒性。然而，关于如何支持NK细胞的维持和功能以获得更好的反应率和更长的持续时间的先进细节仍有待阐明。这篇综述系统地总结了NK细胞在肿瘤发生发展中的深远作用，重点介绍了以NK细胞为靶点的疗法在血液系统恶性肿瘤临床治疗中的最新进展和目前面临的挑战。

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来源期刊

Experimental Hematology & Oncology Medicine-Oncology

CiteScore

12.60

自引率

7.30%

发文量

审稿时长

6 weeks

期刊介绍： Experimental Hematology & Oncology is an open access journal that encompasses all aspects of hematology and oncology with an emphasis on preclinical, basic, patient-oriented and translational research. The journal acts as an international platform for sharing laboratory findings in these areas and makes a deliberate effort to publish clinical trials with 'negative' results and basic science studies with provocative findings. Experimental Hematology & Oncology publishes original work, hypothesis, commentaries and timely reviews. With open access and rapid turnaround time from submission to publication, the journal strives to be a hub for disseminating new knowledge and discussing controversial topics for both basic scientists and busy clinicians in the closely related fields of hematology and oncology.