REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1595533
Recent Advances in Tumor Immunotherapy Based on NK Cells
Provisionally accepted
Mengmeng Chen1
Bing Zhang2Xuanlin Mu3
Bingqiang Zhang1Tielin Yang4Gaofeng Zhang5Yuchao Gu6Bin Pei7
Shaoshuai Liang8*- 1Qingdao Restore Biotechnology Co., Ltd., Qingdao, China
- 2Qilu Hospital, Shandong University, Qingdao, China
- 3Qingdao Cardiovascular Hospital, Qing Dao, China
- 4School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, Shaanxi Province, China
- 5Qingdao Municipal Hospital, Qingdao, Shandong Province, China
- 6Qingdao University of Science and Technology, Qingdao, Shandong Province, China
- 7Xiangyang No.1 People’s Hospital, Hubei University of Medicine, Xiangyang, China
- 8Qingdao Haier Biotechnology Co., Ltd, Qingdao, China
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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 in vitro, limited persistence in vivo, 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.
Keywords: Natural Killer cells, tumor, Immunotherapy, "Off-the-shelf" cell, clinical applications
Received: 18 Mar 2025; Accepted: 04 Jul 2025.
Copyright: © 2025 Chen, Zhang, Mu, Zhang, Yang, Zhang, Gu, Pei and Liang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Shaoshuai Liang, Qingdao Haier Biotechnology Co., Ltd, Qingdao, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.