Abstract
Tumor recurrence is one of the major life-threatening complications after liver transplantation for liver cancer. In addition to the common mechanisms underlying tumor recurrence, another unavoidable problem is that the immunosuppressive therapeutic regimen after transplantation could promote tumor recurrence and metastasis. Transplant oncology is an emerging field that addresses oncological challenges in transplantation. In this context, a comprehensive therapeutic management approach is required to balance the anti-tumor treatment and immunosuppressive status of recipients. Double-negative T cells (DNTs) are a cluster of heterogeneous cells mainly consisting of two subsets stratified by T cell receptor (TCR) type. Among them, TCRαβ+ DNTs are considered to induce immune suppression in immune-mediated diseases, while TCRγδ+ DNTs are widely recognized as tumor killers. As a composite cell therapy, healthy donor-derived DNTs can be propagated to therapeutic numbers in vitro and applied for the treatment of several malignancies without impairing normal tissues or being rejected by the host. In this work, we summarized the biological characteristics and functions of DNTs in oncology, immunology, and transplantation. Based on the multiple roles of DNTs, we propose that a new balance could be achieved in liver transplant oncology using them as an off-the-shelf adoptive cell therapy (ACT).
摘要
肿瘤复发是肝癌肝移植术后危及生命的主要并发症之一. 除了常见的肿瘤复发机制外, 另一个不可避免的问题是移植后的免疫抑制治疗方案可能促进肿瘤复发和转移. 移植肿瘤学是一个新兴领域以解决肝移植相关的肿瘤学问题. 在此背景下, 需要综合治疗管理方法来平衡受者的抗肿瘤治疗和免疫抑制状态. 双阴性T细胞 (DNTs) 是一群异质性细胞, 主要由T细胞受体 (TCR) 不同类型的两个亚群组成. 其中, TCRαβ+ DNTs 被认为在免疫性疾病中诱导免疫抑制, 而 TCRγδ+ DNTs 被广泛认为是肿瘤杀伤细胞. 作为一种复合细胞疗法, 健康供体来源的 DNTs 可在体外增殖至治疗量级, 并应用于多种恶性肿瘤的治疗, 同时既不损伤正常组织, 也不被宿主排斥. 本文就 DNTs 的生物学特性及其在肿瘤学、 免疫学和移植领域等方面的研究进展进行综述. 基于 DNTs 的多重作用, 我们建议将其作为一种现成的过继性细胞治疗 (ACT), 从而为移植肿瘤学提供一种新的平衡.
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Acknowledgments
This work was supported by the Key Research & Development Plan of Zhejiang Province (Nos. 2019C03050 and 2021C03118), the National Key Research and Development Program of China (No. 2021YFA1100500), and the National Natural Science Foundation of China (No. 92159202).
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Zhihang HU: writing–original draft. Modan YANG: data curation and visualization. Xiao XU and Di LU: conceptualization and writing–review & editing. Hao CHEN, Chiyu HE, Zuyuan LIN, Xinyu YANG, Huigang LI, and Wei SHEN: supervision and writing - review & editing. All authors have read and approved the final manuscript, and therefore, have full access to all the data in the study and take responsibility for the integrity and security of the data.
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Zhihang HU, Modan YANG, Hao CHEN, Chiyu HE, Zuyuan LIN, Xinyu YANG, Huigang LI, Wei SHEN, Di LU, and Xiao XU declare that they have no conflict of interest.
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Hu, Z., Yang, M., Chen, H. et al. Double-negative T cells: a promising avenue of adoptive cell therapy in transplant oncology. J. Zhejiang Univ. Sci. B 24, 387–396 (2023). https://doi.org/10.1631/jzus.B2200528
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DOI: https://doi.org/10.1631/jzus.B2200528