Natural Killer Cell Immune Checkpoints and Their Therapeutic Targeting in Cancer Treatment
Natural killer (NK) cells, serving as pivotal mediators of innate immunity, play an important role in antitumor immunity. Immune checkpoint can be expressed on the surface of NK cells and meticulously regulates their activation states and effector functions through complex signaling networks. In rec...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
American Association for the Advancement of Science (AAAS)
2025-01-01
|
| Series: | Research |
| Online Access: | https://spj.science.org/doi/10.34133/research.0723 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850132292534534144 |
|---|---|
| author | Anqi Lin Pengxi Ye Zhengrui Li Aimin Jiang Zaoqu Liu Quan Cheng Jian Zhang Peng Luo |
| author_facet | Anqi Lin Pengxi Ye Zhengrui Li Aimin Jiang Zaoqu Liu Quan Cheng Jian Zhang Peng Luo |
| author_sort | Anqi Lin |
| collection | DOAJ |
| description | Natural killer (NK) cells, serving as pivotal mediators of innate immunity, play an important role in antitumor immunity. Immune checkpoint can be expressed on the surface of NK cells and meticulously regulates their activation states and effector functions through complex signaling networks. In recent years, tumor immunotherapy strategies focusing on NK cell immune checkpoints have demonstrated remarkable advancements. This review systematically elucidates the expression profiles, signaling pathways, and the immune checkpoint molecule regulatory mechanisms localized on the NK cell membrane (e.g., NKG2A, KIRs, and TIGIT) or intracellularly (e.g., BIM, Cbl-b, and EZH2) during tumor immune evasion. Particular attention is devoted to dissecting the regulatory mechanisms through which these immune checkpoint molecules influence NK cell-mediated cytotoxicity, cytokine secretion, proliferative capacity, and tunable modulation of NK cell immune checkpoint expression by diverse factors within the tumor microenvironment. Furthermore, this review comprehensively summarizes preclinical advancements in NK cell immune checkpoint blockade strategies, including single checkpoint blockade, combinatorial checkpoint approaches, and their integration with conventional therapeutic modalities. Additionally, emerging therapeutic advancements, such as gene-editing technologies and chimeric antigen receptor-NK (CAR-NK) cell therapy, are evaluated for their prospective applications in immunotherapy based on NK cells. By thoroughly elucidating the molecular regulatory networks underlying NK cell immune checkpoints and their mechanisms of action within the complex tumor microenvironment, this review aims to provide critical theoretical insights and translational foundations to foster the development of innovative tumor immunotherapy strategies, improvement of combination therapies, and realization of personalized precision medicine. |
| format | Article |
| id | doaj-art-cd95e9d2d0b1454bbe53af128beca5d2 |
| institution | OA Journals |
| issn | 2639-5274 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | Article |
| series | Research |
| spelling | doaj-art-cd95e9d2d0b1454bbe53af128beca5d22025-08-20T02:32:14ZengAmerican Association for the Advancement of Science (AAAS)Research2639-52742025-01-01810.34133/research.0723Natural Killer Cell Immune Checkpoints and Their Therapeutic Targeting in Cancer TreatmentAnqi Lin0Pengxi Ye1Zhengrui Li2Aimin Jiang3Zaoqu Liu4Quan Cheng5Jian Zhang6Peng Luo7Donghai County People’s Hospital—Jiangnan University Smart Healthcare Joint Laboratory, Donghai County People’s Hospital (Affiliated Kangda College of Nanjing Medical University); Department of Oncology, Zhujiang Hospital, Southern Medical University, Lianyungang 222000, China.School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong 510515, China.Department of Oral and Cranio-Maxillofacial Surgery, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, Shanghai 200011, China.Department of Urology, Changhai Hospital, Naval Medical University (Second Military Medical University), Shanghai, China.Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, China.Donghai County People’s Hospital—Jiangnan University Smart Healthcare Joint Laboratory, Donghai County People’s Hospital (Affiliated Kangda College of Nanjing Medical University); Department of Oncology, Zhujiang Hospital, Southern Medical University, Lianyungang 222000, China.Natural killer (NK) cells, serving as pivotal mediators of innate immunity, play an important role in antitumor immunity. Immune checkpoint can be expressed on the surface of NK cells and meticulously regulates their activation states and effector functions through complex signaling networks. In recent years, tumor immunotherapy strategies focusing on NK cell immune checkpoints have demonstrated remarkable advancements. This review systematically elucidates the expression profiles, signaling pathways, and the immune checkpoint molecule regulatory mechanisms localized on the NK cell membrane (e.g., NKG2A, KIRs, and TIGIT) or intracellularly (e.g., BIM, Cbl-b, and EZH2) during tumor immune evasion. Particular attention is devoted to dissecting the regulatory mechanisms through which these immune checkpoint molecules influence NK cell-mediated cytotoxicity, cytokine secretion, proliferative capacity, and tunable modulation of NK cell immune checkpoint expression by diverse factors within the tumor microenvironment. Furthermore, this review comprehensively summarizes preclinical advancements in NK cell immune checkpoint blockade strategies, including single checkpoint blockade, combinatorial checkpoint approaches, and their integration with conventional therapeutic modalities. Additionally, emerging therapeutic advancements, such as gene-editing technologies and chimeric antigen receptor-NK (CAR-NK) cell therapy, are evaluated for their prospective applications in immunotherapy based on NK cells. By thoroughly elucidating the molecular regulatory networks underlying NK cell immune checkpoints and their mechanisms of action within the complex tumor microenvironment, this review aims to provide critical theoretical insights and translational foundations to foster the development of innovative tumor immunotherapy strategies, improvement of combination therapies, and realization of personalized precision medicine.https://spj.science.org/doi/10.34133/research.0723 |
| spellingShingle | Anqi Lin Pengxi Ye Zhengrui Li Aimin Jiang Zaoqu Liu Quan Cheng Jian Zhang Peng Luo Natural Killer Cell Immune Checkpoints and Their Therapeutic Targeting in Cancer Treatment Research |
| title | Natural Killer Cell Immune Checkpoints and Their Therapeutic Targeting in Cancer Treatment |
| title_full | Natural Killer Cell Immune Checkpoints and Their Therapeutic Targeting in Cancer Treatment |
| title_fullStr | Natural Killer Cell Immune Checkpoints and Their Therapeutic Targeting in Cancer Treatment |
| title_full_unstemmed | Natural Killer Cell Immune Checkpoints and Their Therapeutic Targeting in Cancer Treatment |
| title_short | Natural Killer Cell Immune Checkpoints and Their Therapeutic Targeting in Cancer Treatment |
| title_sort | natural killer cell immune checkpoints and their therapeutic targeting in cancer treatment |
| url | https://spj.science.org/doi/10.34133/research.0723 |
| work_keys_str_mv | AT anqilin naturalkillercellimmunecheckpointsandtheirtherapeutictargetingincancertreatment AT pengxiye naturalkillercellimmunecheckpointsandtheirtherapeutictargetingincancertreatment AT zhengruili naturalkillercellimmunecheckpointsandtheirtherapeutictargetingincancertreatment AT aiminjiang naturalkillercellimmunecheckpointsandtheirtherapeutictargetingincancertreatment AT zaoquliu naturalkillercellimmunecheckpointsandtheirtherapeutictargetingincancertreatment AT quancheng naturalkillercellimmunecheckpointsandtheirtherapeutictargetingincancertreatment AT jianzhang naturalkillercellimmunecheckpointsandtheirtherapeutictargetingincancertreatment AT pengluo naturalkillercellimmunecheckpointsandtheirtherapeutictargetingincancertreatment |