College of Medicine, University of Central Florida, Orlando, FL, United States.
Burnett School of Biomedical Science, College of Medicine, University of Central Florida, Orlando, FL, United States.
Front Immunol. 2021 Apr 28;12:679117. doi: 10.3389/fimmu.2021.679117. eCollection 2021.
Cancer immunotherapy is a highly successful and rapidly evolving treatment modality that works by augmenting the body's own immune system. While various immune stimulation strategies such as PD-1/PD-L1 or CTLA-4 checkpoint blockade result in robust responses, even in patients with advanced cancers, the overall response rate is low. While immune checkpoint inhibitors are known to enhance cytotoxic T cells' antitumor response, current evidence suggests that immune responses independent of cytotoxic T cells, such as Natural Killer (NK) cells, play crucial role in the efficacy of immunotherapeutic interventions. NK cells hold a distinct role in potentiating the innate immune response and activating the adaptive immune system. This review highlights the importance of the early actions of the NK cell response and the pivotal role NK cells hold in priming the immune system and setting the stage for successful response to cancer immunotherapy. Yet, in many patients the NK cell compartment is compromised thus lowering the chances of successful outcomes of many immunotherapies. An overview of mechanisms that can drive NK cell dysfunction and hinder immunotherapy success is provided. Rather than relying on the likely dysfunctional endogenous NK cells to work with immunotherapies, adoptive allogeneic NK cell therapies provide a viable solution to increase response to immunotherapies. This review highlights the advances made in development of NK cell therapeutics for clinical application with evidence supporting their combinatorial application with other immune-oncology approaches to improve outcomes of immunotherapies.
癌症免疫疗法是一种非常成功且快速发展的治疗方式,通过增强身体自身的免疫系统来发挥作用。虽然各种免疫刺激策略,如 PD-1/PD-L1 或 CTLA-4 检查点阻断,会导致强烈的反应,甚至在晚期癌症患者中也是如此,但总体反应率仍然较低。虽然免疫检查点抑制剂已被证明可增强细胞毒性 T 细胞的抗肿瘤反应,但目前的证据表明,细胞毒性 T 细胞以外的免疫反应,如自然杀伤 (NK) 细胞,在免疫治疗干预的疗效中起着至关重要的作用。NK 细胞在增强先天免疫反应和激活适应性免疫系统方面具有独特的作用。这篇综述强调了 NK 细胞反应的早期作用的重要性,以及 NK 细胞在启动免疫系统和为癌症免疫治疗的成功反应奠定基础方面所起的关键作用。然而,在许多患者中,NK 细胞群受到损害,从而降低了许多免疫疗法成功的机会。提供了一种概述可以驱动 NK 细胞功能障碍并阻碍免疫治疗成功的机制。与其依赖可能功能失调的内源性 NK 细胞与免疫疗法一起工作,同种异体 NK 细胞过继疗法提供了一种可行的解决方案,以增加对免疫疗法的反应。这篇综述强调了开发用于临床应用的 NK 细胞治疗的进展,并提供了支持它们与其他免疫肿瘤学方法联合应用以改善免疫疗法效果的证据。
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