{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T08:59:11Z","timestamp":1793350751587,"version":"4.5.0"},"reference-count":113,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    As early as 1863, Virchow observed that cancer often arises at sites of chronic inflammation. Modern epidemiological and clinical studies have confirmed the link between inflammation and cancer. Natural Killer (NK) cells actively participate in and regulate inflammatory processes; however, they are not strictly classified as classic \u2018inflammatory cells\u2019 in cellular taxonomy. NK cells rapidly identify and eliminate malignantly transformed cells in a non-major histocompatibility complex (MHC)-restricted manner, a characteristic that distinguishes them from other immune cells. Furthermore, their use in allogeneic settings carries a very low risk of graft-versus-host disease (GvHD), making them ideal candidates for developing \u2018off-the-shelf\u2019 cellular immunotherapies. Although early clinical attempts using unmodified NK cells showed limited efficacy, the past decade has witnessed rapid advancements in genetic engineering, cell expansion and differentiation, and synthetic biology, propelling NK cell therapy into a new era of development. This article aims to provide a systematic and multi-dimensional review of the latest research progress in NK cell therapy. We begin by revisiting the core biological basis of NK cell anti-tumor activity, focusing on design strategies, clinical breakthroughs, and bottlenecks of Chimeric Antigen Receptor NK (CAR-NK) cell therapy in hematological malignancies and solid tumors. We delve into antibody-based NK cell recruitment strategies (such as BiKEs\/TriKEs) and techniques to enhance antibody-dependent cellular cytotoxicity (ADCC), and analyze cytokine-induced memory-like NK (CIML-NK) cells as a non-gene editing enhancement strategy. Simultaneously, we focus on the core challenges currently faced by NK cell therapies, particularly in solid tumors, including poor tumor infiltration, potent suppression by the tumor microenvironment (TME), and limited\n                    <jats:italic>in vivo<\/jats:italic>\n                    persistence. We summarize diversified synergistic strategies, such as combination with immune checkpoint inhibitors, radiotherapy, chemotherapy, targeted drugs, and direct modifications of the TME. Finally, this article discusses contentious points within the field and provides a forward-looking perspective on future directions, striving to offer a comprehensive and insightful reference for the translation of NK cell therapy from the laboratory to widespread clinical application.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1795143","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T05:54:27Z","timestamp":1777442067000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["A new era of natural killer cell immunotherapy in tumor treatment: latest advances and cutting-edge perspectives from basic research to clinical practice"],"prefix":"10.3389","volume":"17","author":[{"given":"Xin","family":"Du","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine, First Hospital of Shanxi Medical University","place":["Taiyuan, China"]},{"name":"Collaborative Innovation Center for Molecular Imaging of Precision Medicine, Shanxi Medical University","place":["Taiyuan, China"]},{"name":"China Atomic Energy Authority (CAEA) Center of Excellence on Nuclear Technology Applications for the Diagnosis, Treatment & Transformation of Nuclear Medicine","place":["Taiyuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shixin","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, First Hospital of Shanxi Medical University","place":["Taiyuan, China"]},{"name":"Collaborative Innovation Center for Molecular Imaging of Precision Medicine, Shanxi Medical University","place":["Taiyuan, China"]},{"name":"China Atomic Energy Authority (CAEA) Center of Excellence on Nuclear Technology Applications for the Diagnosis, Treatment & Transformation of Nuclear Medicine","place":["Taiyuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, First Hospital of Shanxi Medical University","place":["Taiyuan, China"]},{"name":"Collaborative Innovation Center for Molecular Imaging of Precision Medicine, Shanxi Medical University","place":["Taiyuan, China"]},{"name":"China Atomic Energy Authority (CAEA) Center of Excellence on Nuclear Technology Applications for the Diagnosis, Treatment & Transformation of Nuclear Medicine","place":["Taiyuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J 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