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MINI REVIEW article
Front. Oncol.
Sec. Cancer Immunity and Immunotherapy
Volume 14 - 2024 |
doi: 10.3389/fonc.2024.1502270
This article is part of the Research Topic Integrating Molecular Mechanisms, Immunotherapy, and Drug Sensitivity in Cancer Immunology and Oncology View all 11 articles
Reversing NK cell exhaustion: a novel strategy combining immune checkpoint blockade with drug sensitivity enhancement in the treatment of hepatocellular carcinoma
Provisionally accepted
Huang Yuxiang
1
Huang Junqi
1*
Liao Hengjian
1*
Luo Jiefu
1*
Wei Huaning
1*
Li Anling
1*
Lu Yujie
1
Xiang Bangde
1*
Xie Yuan
2*- 1 Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 5 530021, China, Nanning, China
- 2 Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor,Ministry 7 of Education, Nanning 530021, China, Nanning, China
Hepatocellular carcinoma (HCC) is one of the most common lethal cancers worldwide. Natural killer cells (NK cells) play a key role in liver immunosurveillance, but in the tumor microenvironment, NK cells are readily depleted, as evidenced by down-regulation of activating receptors, reduced cytokine secretion, and attenuated killing function. The up-regulation of inhibitory receptors, such as PD-1, TIM-3, and LAG-3, further exacerbates the depletion of NK cells. Combined blockade strategies targeting these immunosuppressive mechanisms, such as the combination of PD-1 inhibitors with other inhibitory pathways (eg. TIM-3 and LAG-3), have shown potential to reverse NK cell exhaustion in preclinical studies. This article explores the promise of these innovative strategies in HCC immunotherapy, providing new therapeutic directions for optimizing NK cell function and improving drug sensitivity.
Keywords: Hepatocellular Carcinoma, NK cell exhaustion, Immunotherapy, Immune checkpoint blockade, drug sensitivity, Tumor Microenvironment, Oncology drug innovation
Received: 26 Sep 2024; Accepted: 20 Dec 2024.
Copyright: © 2024 Yuxiang, Junqi, Hengjian, Jiefu, Huaning, Anling, Yujie, Bangde and Yuan. 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:
Huang Junqi, Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 5 530021, China, Nanning, China
Liao Hengjian, Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 5 530021, China, Nanning, China
Luo Jiefu, Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 5 530021, China, Nanning, China
Wei Huaning, Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 5 530021, China, Nanning, China
Li Anling, Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 5 530021, China, Nanning, China
Xiang Bangde, Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning 5 530021, China, Nanning, China
Xie Yuan, Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor,Ministry 7 of Education, Nanning 530021, China, Nanning, China
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