Chen Mengmeng, Zhang Bing, Mu Xuanlin, Zhang Bingqiang, Yang Tielin, Zhang Gaofeng, Gu Yuchao, Pei Bin, Liang Shaoshuai
Research Institute, Qingdao Restore Biotechnology Co., Ltd., Qingdao, Shandong, China.
Research and Development Department (R&D), Key Laboratory of Cancer and Immune Cells of Qingdao, Qingdao, Shandong, China.
Front Immunol. 2025 Aug 7;16:1595533. doi: 10.3389/fimmu.2025.1595533. eCollection 2025.
Immunotherapy has emerged as the established fourth pillar of cancer treatment following surgery, radiotherapy, and chemotherapy, representing a cutting-edge research domain in translational medicine and clinical oncology. Natural killer (NK) cells, a type of innate cytotoxic lymphocyte, possess unique antitumor properties that are independent of major histocompatibility complex (MHC) restrictions, making them promising candidates for "off-the-shelf" therapeutic products. NK cells can eliminate tumor cells through various mechanisms. Genetic engineering of NK cells can enhance their activation signals, promote proliferation, inhibit suppressive signals, and improve tumor homing, all of which are expected to significantly boost their clinical efficacy. Compared to chimeric antigen receptor T (CAR-T) cell therapy, NK cell-based immunotherapy demonstrates superior safety and tolerability. However, the clinical application of NK cells still faces several challenges, including suboptimal expansion efficiency , limited persistence , low transduction efficiency of chimeric antigen receptor NK (CAR-NK) cells, and immunosuppressive effects of the tumor microenvironment. These issues require further investigation to achieve significant improvements. This review provides a comprehensive overview of the biological characteristics of NK cells, their antitumor mechanisms, the latest therapeutic strategies in tumor immunotherapy, and the challenges associated with NK cell-based immunotherapy, aiming to offer valuable insights for future research and clinical applications.
免疫疗法已成为继手术、放疗和化疗之后公认的癌症治疗第四大支柱，是转化医学和临床肿瘤学领域的前沿研究方向。自然杀伤（NK）细胞是一种先天性细胞毒性淋巴细胞，具有独特的抗肿瘤特性，不受主要组织相容性复合体（MHC）限制，这使其成为 “现货” 治疗产品的理想候选者。NK细胞可通过多种机制消除肿瘤细胞。对NK细胞进行基因工程改造可增强其激活信号、促进增殖、抑制抑制信号并改善肿瘤归巢，所有这些都有望显著提高其临床疗效。与嵌合抗原受体T（CAR-T）细胞疗法相比，基于NK细胞的免疫疗法具有更高的安全性和耐受性。然而，NK细胞的临床应用仍面临诸多挑战，包括扩增效率欠佳、持久性有限、嵌合抗原受体NK（CAR-NK）细胞转导效率低以及肿瘤微环境的免疫抑制作用。这些问题需要进一步研究以实现显著改善。本综述全面概述了NK细胞的生物学特性、其抗肿瘤机制、肿瘤免疫治疗的最新策略以及基于NK细胞的免疫治疗相关挑战，旨在为未来研究和临床应用提供有价值的见解。
