{"title":"Interfering with KIR and NKG2A immune checkpoint axes to unleash NK cell immunotherapy","authors":"","doi":"10.1016/j.beha.2024.101568","DOIUrl":null,"url":null,"abstract":"<div><p>Due to their intrinsic ability to eliminate malignant cells, natural killer (NK) cells emerge as a promising immunotherapy for cancer. While clinical studies have affirmed the safety of NK cell infusions and combination therapies have demonstrated encouraging outcomes in hematological malignancies, the efficacy of NK cell immunotherapeutic interventions remains heterogeneous across patient cohorts. Moreover, the implementation of NK cell immunotherapy in solid tumors presents notable challenges. Interfering with key NK cell inhibitory signaling pathways by targeting inhibitory killer cell immunoglobulin-like receptors (KIRs) and CD94/NK group 2 member A (NKG2A), holds promise for unleashing the full potential of NK cell-based immunotherapy. In this review, we provide an overview of the current approaches for interfering with inhibitory KIR and NKG2A signaling, exploring a selection of the multitude of combination strategies available. We discuss the significance of maintaining the delicate balance between achieving optimal suppression of NK cell inhibition and ensuring effective activation of anti-tumor effector function, while preserving the favorable safety profiles. The consideration of strategies to modulate inhibitory signaling pathways associated with KIR and NKG2A presents promising avenues for enhancing the efficacy of NK cell immunotherapy.</p></div>","PeriodicalId":8744,"journal":{"name":"Best Practice & Research Clinical Haematology","volume":null,"pages":null},"PeriodicalIF":2.2000,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Best Practice & Research Clinical Haematology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1521692624000343","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Due to their intrinsic ability to eliminate malignant cells, natural killer (NK) cells emerge as a promising immunotherapy for cancer. While clinical studies have affirmed the safety of NK cell infusions and combination therapies have demonstrated encouraging outcomes in hematological malignancies, the efficacy of NK cell immunotherapeutic interventions remains heterogeneous across patient cohorts. Moreover, the implementation of NK cell immunotherapy in solid tumors presents notable challenges. Interfering with key NK cell inhibitory signaling pathways by targeting inhibitory killer cell immunoglobulin-like receptors (KIRs) and CD94/NK group 2 member A (NKG2A), holds promise for unleashing the full potential of NK cell-based immunotherapy. In this review, we provide an overview of the current approaches for interfering with inhibitory KIR and NKG2A signaling, exploring a selection of the multitude of combination strategies available. We discuss the significance of maintaining the delicate balance between achieving optimal suppression of NK cell inhibition and ensuring effective activation of anti-tumor effector function, while preserving the favorable safety profiles. The consideration of strategies to modulate inhibitory signaling pathways associated with KIR and NKG2A presents promising avenues for enhancing the efficacy of NK cell immunotherapy.
自然杀伤(NK)细胞具有消除恶性细胞的内在能力,因此成为一种很有前景的癌症免疫疗法。虽然临床研究证实了输注 NK 细胞的安全性,而且联合疗法在血液恶性肿瘤中也取得了令人鼓舞的结果,但 NK 细胞免疫治疗干预措施在不同患者群中的疗效仍然参差不齐。此外,在实体瘤中实施 NK 细胞免疫疗法也面临着显著的挑战。通过靶向抑制性杀伤细胞免疫球蛋白样受体(KIR)和 CD94/NK 2 组 A 成员(NKG2A)来干扰关键的 NK 细胞抑制信号通路,有望充分释放基于 NK 细胞的免疫疗法的潜力。在这篇综述中,我们概述了目前干扰抑制性 KIR 和 NKG2A 信号传导的方法,并探讨了现有的多种组合策略。我们讨论了在实现对 NK 细胞最佳抑制和确保有效激活抗肿瘤效应功能之间保持微妙平衡的重要性,同时保持良好的安全性。考虑调节与 KIR 和 NKG2A 相关的抑制信号通路的策略为提高 NK 细胞免疫疗法的疗效带来了希望。
期刊介绍:
Best Practice & Research Clinical Haematology publishes review articles integrating the results from the latest original research articles into practical, evidence-based review articles. These articles seek to address the key clinical issues of diagnosis, treatment and patient management. Each issue follows a problem-orientated approach which focuses on the key questions to be addressed, clearly defining what is known and not known, covering the spectrum of clinical and laboratory haematological practice and research. Although most reviews are invited, the Editor welcomes suggestions from potential authors.