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

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

Author: Zhihang HU ¹ ; Modan YANG ¹ ; Hao CHEN ¹ ; Chiyu HE ¹ ; Zuyuan LIN ¹ ; Xinyu YANG ¹ ; Huigang LI ¹ ; Wei SHEN ¹ ; Di LU ² ; Xiao XU ³
Author Information

1. Zhejiang University School of Medicine, Hangzhou 310058, China.
2. Zhejiang University School of Medicine, Hangzhou 310058, China. zjuludi@zju.edu.cn.
3. Zhejiang University School of Medicine, Hangzhou 310058, China. zjxu@zju.edu.cn.
Publication Type:Journal Article
Keywords: Adoptive cell therapy (ACT); Double-negative T cell (DNT); Liver cancer; Liver transplantation; Oncology
MeSH: Humans; T-Lymphocytes; Immunotherapy, Adoptive; Neoplasm Recurrence, Local; Transplantation, Homologous; Cell- and Tissue-Based Therapy
From: Journal of Zhejiang University. Science. B 2023;24(5):387-396
CountryChina
Language:English
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).