Double-negative T cells: a promising avenue of adoptive cell therapy in transplant oncology

Zhihang HU; Modan YANG; Hao CHEN; Chiyu HE; Zuyuan LIN; Xinyu YANG; Huigang LI; Wei SHEN; Di LU; Xiao XU

doi:10.1631/jzus.B2200528

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Mini-review | Updated：2023-05-15

Double-negative T cells: a promising avenue of adoptive cell therapy in transplant oncology
Double-negative T cells: a promising avenue of adoptive cell therapy in transplant oncology
双阴性T细胞：移植肿瘤学中一种颇具前景的过继细胞疗法
Journal of Zhejiang University-SCIENCE B(Biomedicine & Biotechnology) Vol. 24, Issue 5, Pages: 387-396(2023)
Affiliations：

1.Zhejiang University School of Medicine, Hangzhou 310058, China
2.Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China
3.Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou 310006, China
4.Institute of Organ Transplantation, Zhejiang University, Hangzhou 310003, China
5.NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou 310003, China
6.Department of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital, Hangzhou 310004, China
Funds：
DOI：10.1631/jzus.B2200528
CLC：
CSTR：
Received：17 October 2022，

Revised：2023-02-19，

Published：15 May 2023
Accepted：

胡志航,杨墨丹,陈昊等.双阴性T细胞：移植肿瘤学中一种颇具前景的过继细胞疗法[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2023,24(05):387-396.

Zhihang HU, Modan YANG, Hao CHEN, et al. Double-negative T cells: a promising avenue of adoptive cell therapy in transplant oncology[J]. Journal of Zhejiang University-SCIENCE B(Biomedicine & Biotechnology), 2023, 24(5): 387-396.
胡志航,杨墨丹,陈昊等.双阴性T细胞：移植肿瘤学中一种颇具前景的过继细胞疗法[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2023,24(05):387-396. DOI： 10.1631/jzus.B2200528.

Zhihang HU, Modan YANG, Hao CHEN, et al. Double-negative T cells: a promising avenue of adoptive cell therapy in transplant oncology[J]. Journal of Zhejiang University-SCIENCE B(Biomedicine & Biotechnology), 2023, 24(5): 387-396. DOI： 10.1631/jzus.B2200528.

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。

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).

关键词

Keywords

references

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