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Journal of Zhejiang University SCIENCE B
ISSN 1673-1581(Print), 1862-1783(Online), Monthly
2023 Vol.24 No.5 P.387-396
Double-negative T cells: a promising avenue of adoptive cell therapy in transplant oncology
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).
Key words: Double-negative T cell (DNT); Adoptive cell therapy (ACT); Liver cancer; Liver transplantation; Oncology
机构：1中国地质科学院，中国北京，100037；2中国地质大学（北京），水资源与环境学院，中国北京，100083；3中国地质调查局西安地质调查中心，中国西安，710054；4中国地质调查局成都地质调查中心，中国成都，610081
目的：基于压汞法（MIP）的6种分形模型常被用来研究多孔介质的分形特征，但是这些模型中的大多数并不能直接适用于黄土的小微孔，且小微孔隙对水的渗流吼道有显著影响。本文旨在结合常规变水头渗透试验、MIP分析和扫描电镜（SEM）图像等，研究小微孔及其饱和渗透特性，并验证6种MIP分形模型是否可用于评估原状黄土的微结构类型和饱和渗透特征。
创新点：1.结合饱和渗透系数和SEM图像计盒维数等参数进行相关性分析和显著性检验，以确定最适合黄土小微孔的MIP分形模型；2.建立SEM分形维数和MIP分形维数的耦合，并结合黏粒含量，对原状黄土微结构类型进行分类和对饱和渗透系数从1×10?4cm/s变到1×10?5cm/s进行评价。
方法：1.通过压汞试验和6种MIP分形模型公式，得出原状黄土小微孔隙在不同分形模型下的分形维数。2.通过SEM图像和计盒维数计算得出原状黄土小微孔隙的二维分形维数。
结论：1.模型2（Neimark模型）对小微孔隙显示出非常好的线性拟合（拟合系数大于0.94）；其分形维数值与黏土含量、密度和饱和渗透系数呈强正相关，并与SEM图像的计盒维数相匹配。2.黏土颗粒含量高会导致小微孔数量增加；这些小微孔会导致孔隙结构的表面粗糙度和不均匀性增加，从而呈现出较大的分形维数；这一过程最终导致大中孔隙和主导流线减少，从而降低饱和渗透性。3.本研究提出了新的分维椭圆及其面积比（*EAR）参数，其中两个主要的半轴由Neimark模型的结果（减2）和计盒维数（减1）组成；*EAR和黏土含量可作为定量评价黄土微结构类型和饱和渗透性的有效参数；当*EAR在35%至50%之间、黏土含量在9%至15%之间时，原状黄土微观结构从Ⅰ型转变为Ⅱ型；当*EAR大于50%、黏土含量大于15%时，微结构进一步从Ⅱ型转变为Ⅲ型；相应地，饱和渗透系数从1×10?4cm/s转变为1×10?5cm/s。
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DOI:
10.1631/jzus.B2200528
CLC number:
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On-line Access:
2023-05-15
Received:
2022-10-17
Revision Accepted:
2023-02-19
Crosschecked:
2023-05-16