研究概要
自然杀伤(NK)细胞是固有免疫系统的关键效应细胞。
中文摘要
自然杀伤(NK)细胞是先天免疫系统的关键效应细胞,无需抗原预先致敏即可识别并清除恶性细胞,因此在肿瘤免疫治疗中受到广泛关注。NK细胞疗法在多种血液系统恶性肿瘤中显示较一致的临床活性,但在实体瘤中的疗效差异很大,给临床转化带来显著挑战。本综述总结NK细胞的生物学特征及抗肿瘤机制,并根据已发表临床证据,综合描述其治疗乳腺癌、卵巢癌、黑色素瘤等实体瘤及血液系统恶性肿瘤的疗效异质性。NK细胞疗效差异主要源于多种因素:肿瘤微环境(TME)免疫抑制、肿瘤浸润能力不足、靶抗原表达异质,以及抑制性受体信号。此外,产品特征——包括细胞来源、基因工程策略、体外扩增方案、预处理方案及剂量——也显著影响治疗结局。未来NK细胞免疫治疗的开发应聚焦于基于机制的患者选择及合理设计联合治疗,以推动其持续转化为精准肿瘤学实践。
展开英文摘要原文
Natural killer (NK) cells are pivotal effector cells of the innate immune system. Their capacity to recognize and eliminate malignant cells without requiring antigen priming has attracted considerable interest in tumor immunotherapy. While NK cell therapy has shown relatively consistent clinical activity across various hematologic malignancies, its efficacy in solid tumors remains highly variable, posing significant challenges for clinical translation. This review summarizes the biological characteristics and antitumor mechanisms of NK cells. Based on published clinical evidence, it describes and synthesizes the heterogeneity in therapeutic efficacy across both solid tumors-including breast cancer (BC), ovarian cancer (OC), and melanoma (MEL)-and hematologic malignancies. The findings indicate that NK cell efficacy heterogeneity arises primarily from multiple factors: immunosuppression within the tumor microenvironment (TME), inadequate tumor infiltration capacity, heterogeneity in target antigen expression, and inhibitory receptor signaling. In addition, product-related attributes-including cell source, genetic engineering strategies, ex vivo expansion protocols, pretreatment regimens, and dosage-substantially influence therapeutic outcomes. Moving forward, the development of NK cell immunotherapy should focus on mechanism-informed patient selection and the rational design of combination therapy to facilitate sustained translation into precision oncology practice.
论文信息
- 作者
- Wang Y、Yu Y、Wang S、Qu J、Song Y
- 第一作者单位
- College of Life Sciences, Yantai University, Yantai 264005, Shandong, China.China
- 通讯作者单位
- College of Life Sciences, Yantai University, Yantai 264005, Shandong, China. Electronic address: songyizhe@ytu.edu.cn.China
- 文献类型
- 综述
- 期刊
- International immunopharmacology2026 Apr 1