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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
Chinese Summary <293> 基于压汞试验的黄土小微孔分维分析及渗透评价
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。
关键词组：
References:
[1]AchitaP, DervovicD, LyD, et al., 2018. Infusion of ex-vivo expanded human TCR-αβ+ double-negative regulatory T cells delays onset of xenogeneic graft-versus-host disease. Clin Exp Immunol, 193(3):386-399.
[2]AlmeidaCF, SmithDGM, ChengTY, et al., 2021. Benzofuran sulfonates and small self-lipid antigens activate type II NKT cells via CD1d. Proc Natl Acad Sci USA, 118(34):e2104420118.
[3]BaforEE, ValenciaJC, YoungHA, 2022. Double negative T regulatory cells: an emerging paradigm shift in reproductive immune tolerance? Front Immunol, 13:886645.
[4]BroutierL, MastrogiovanniG, VerstegenMMA, et al., 2017. Human primary liver cancer-derived organoid cultures for disease modeling and drug screening. Nat Med, 23(12):1424-1435.
[5]CapsomidisA, BenthallG, van AckerHH, et al., 2018. Chimeric antigen receptor-engineered human gamma delta T cells: enhanced cytotoxicity with retention of cross presentation. Mol Ther, 26(2):354-365.
[6]ChakravertyR, TeshimaT, 2021. Graft-versus-host disease: a disorder of tissue regeneration and repair. Blood, 138(18):1657-1665.
[7]ChenB, LeeJB, KangH, et al., 2018. Targeting chemotherapy-resistant leukemia by combining DNT cellular therapy with conventional chemotherapy. J Exp Clin Cancer Res, 37:88.
[8]ChenJ, HuPB, WuGH, et al., 2019. Antipancreatic cancer effect of DNT cells and the underlying mechanism. Pancreatology, 19(1):105-113.
[9]ChenWH, ZhouDJ, TorrealbaJR, et al., 2005. Donor lymphocyte infusion induces long-term donor-specific cardiac xenograft survival through activation of recipient double-negative regulatory T cells. J Immunol, 175(5):3409-3416.
[10]ChowdharyVR, KrogmanA, TilahunAY, et al., 2017. Concomitant disruption of CD4 and CD8 genes facilitates the development of double negative αβTCR+ peripheral T cells that respond robustly to staphylococcal superantigen. J Immunol, 198(1):4413-4424.
[11]CrosbyCM, KronenbergM, 2018. Tissue-specific functions of invariant natural killer T cells. Nat Rev Immunol, 18(9):559-574.
[12]de GassartA, LeKS, BruneP, et al., 2021. Development of ICT01, a first-in-class, anti-BTN3A antibody for activating Vγ9Vδ2 T cell-mediated antitumor immune response. Sci Transl Med, 13(616):eabj0835.
[13]DepilS, DuchateauP, GruppSA, et al., 2020. ‘Off-the-shelf’ allogeneic CAR T cells: development and challenges. Nat Rev Drug Discov, 19(3):185-199.
[14]FangLN, LyD, WangSS, et al., 2019. Targeting late-stage non-small cell lung cancer with a combination of DNT cellular therapy and PD-1 checkpoint blockade. J Exp Clin Cancer Res, 38:123.
[15]FischerK, VoelklS, HeymannJ, et al., 2005. Isolation and characterization of human antigen-specific TCRαβ+ CD4-CD8- double-negative regulatory T cells. Blood, 105(7):2828-2835.
[16]FordMS, YoungKJ, ZhangZX, et al., 2002. The immune regulatory function of lymphoproliferative double negative T cells in vitro and in vivo. J Exp Med, 196(2):261-267.
[17]GalluzziL, ChanTA, KroemerG, et al., 2018. The hallmarks of successful anticancer immunotherapy. Sci Transl Med, 10(459):eaat7807.
[18]GálvezNMS, BohmwaldK, PachecoGA, et al., 2021. Type I natural killer T cells as key regulators of the immune response to infectious diseases. Clin Microbiol Rev, 34(2):e00232-20.
[19]HibiT, SapisochinG, 2019. What is transplant oncology? Surgery, 165(2):281-285.
[20]HibiT, ItanoO, ShinodaM, et al., 2017. Liver transplantation for hepatobiliary malignancies: a new era of “Transplant Oncology” has begun. Surg Today, 47(4):403-415.
[21]HoeresT, SmetakM, PretscherD, et al., 2018. Improving the efficiency of Vγ9Vδ2 T-Cell immunotherapy in cancer. Front Immunol, 9:800.
[22]HsuJ, KrishnanA, LeeSA, et al., 2021. CD3+CD4-CD8- double-negative αβ T cells attenuate lung ischemia-reperfusion injury. J Thorac Cardiovasc Surg, 161(1):E81-E90.
[23]HuSH, ZhangLH, GaoJ, et al., 2021. NKG2D enhances double-negative T cell regulation of B cells. Front Immunol, 12:650788.
[24]JuvetSC, ZhangL, 2012. Double negative regulatory T cells in transplantation and autoimmunity: recent progress and future directions. J Mol Cell Biol, 4(1):48-58.
[25]KabelitzD, SerranoR, KouakanouL, et al., 2020. Cancer immunotherapy with γδ T cells: many paths ahead of us. Cell Mol Immunol, 17(9):925-939.
[26]KhanAA, LiuZK, XuX, 2021. Recent advances in immunotherapy for hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int, 20(6):511-520.
[27]Kjer-NielsenL, CorbettAJ, ChenZJ, et al., 2018. An overview on the identification of MAIT cell antigens. Immunol Cell Biol, 96(6):573-587.
[28]LeeJB, MindenMD, ChenWC, et al., 2018. Allogeneic human double negative T cells as a novel immunotherapy for acute myeloid leukemia and its underlying mechanisms. Clin Cancer Res, 24(2):370-382.
[29]LeeJB, KangH, FangLN, et al., 2019. Developing allogeneic double-negative T cells as a novel off-the-shelf adoptive cellular therapy for cancer. Clin Cancer Res, 25(7):2241-2253.
[30]LegouxF, SalouM, LantzO, 2017. Unconventional or preset αβ T cells: evolutionarily conserved tissue-resident T cells recognizing nonpeptidic ligands. Annu Rev Cell Dev Biol, 33:511-535.
[31]LingSB, ZhanQF, JiangGJ, et al., 2022. E2F7 promotes mammalian target of rapamycin inhibitor resistance in hepatocellular carcinoma after liver transplantation. Am J Transplant, 22(10):2323-2336.
[32]LiuYX, ZhangC, 2020. The role of human γδ T cells in anti-tumor immunity and their potential for cancer immunotherapy. Cells, 9(5):1206.
[33]LuJQ, LiuJY, LiA, 2022. Roles of neutrophil reactive oxygen species (ROS) generation in organ function impairment in sepsis. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 23(6):437-450.
[34]LuY, HuPB, ZhouHB, et al., 2019. Double-negative T cells inhibit proliferation and invasion of human pancreatic cancer cells in co-culture. Anticancer Res, 39(11):5911-5918.
[35]MarabelleA, TselikasL, de BaereT, et al., 2017. Intratumoral immunotherapy: using the tumor as the remedy. Ann Oncol, 28:xii33-xii43.
[36]MazzaferroV, RegaliaE, DociR, et al., 1996. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med, 334(11):693-700.
[37]MerimsS, LiX, JoeB, et al., 2011. Anti-leukemia effect of ex vivo expanded DNT cells from AML patients: a potential novel autologous T-cell adoptive immunotherapy. Leukemia, 25(9):1415-1422.
[38]MizukoshiE, KanekoS, 2019. Immune cell therapy for hepatocellular carcinoma. J Hematol Oncol, 12:52.
[39]Newman-RiveraAM, KurzhagenJT, RabbH, 2022. TCRαβ+ CD4-/CD8- “double negative” T cells in health and disease-implications for the kidney. Kidney Int, 102(1):25-37.
[40]NordnessMF, HamelS, GodfreyCM, et al., 2020. Fatal hepatic necrosis after nivolumab as a bridge to liver transplant for HCC: are checkpoint inhibitors safe for the pretransplant patient? Am J Transplant, 20(3):879-883.
[41]PauzaCD, LiouML, LahusenT, et al., 2018. Gamma delta T cell therapy for cancer: it is good to be local. Front Immunol, 9:1305.
[42]PellicciDG, UldrichAP, 2018. Unappreciated diversity within the pool of CD1d-restricted T cells. Semin Cell Dev Biol, 84:42-47.
[43]PonzettaA, CarrieroR, CarnevaleS, et al., 2019. Neutrophils driving unconventional T cells mediate resistance against murine sarcomas and selected human tumors. Cell, 178(2):346-360.e24.
[44]RaoulJL, FornerA, BolondiL, et al., 2019. Updated use of TACE for hepatocellular carcinoma treatment: how and when to use it based on clinical evidence. Cancer Treat Rev, 72:28-36.
[45]RoncaV, WoottonG, MilaniC, et al., 2020. The immunological basis of liver allograft rejection. Front Immunol, 11:2155.
[46]SoaresF, ChenB, LeeJB, et al., 2021. CRISPR screen identifies genes that sensitize AML cells to double-negative T-cell therapy. Blood, 137(16):2171-2181.
[47]StrippoliS, FanizziA, NegriA, et al., 2021. Examining the relationship between circulating CD4-CD8- double-negative T cells and outcomes of immuno-checkpoint inhibitor therapy—looking for biomarkers and therapeutic targets in metastatic melanoma. Cells, 10(2):406.
[48]SunH, CaoS, MashlRJ, et al., 2021. Comprehensive characterization of 536 patient-derived xenograft models prioritizes candidatesfor targeted treatment. Nat Commun, 12:5086.
[49]TakadaY, ItoT, UedaM, et al., 2007. Living donor liver transplantation for patients with HCC exceeding the Milan criteria: a proposal of expanded criteria. Dig Dis, 25(4):299-302.
[50]ThommenDS, SchumacherTN, 2018. T cell dysfunction in cancer. Cancer Cell, 33(4):547-562.
[51]TuvesonD, CleversH, 2019. Cancer modeling meets human organoid technology. Science, 364(6444):952-955.
[52]VasicD, LeeJB, LeungY, et al., 2022. Allogeneic double-negative CAR-T cells inhibit tumor growth without off-tumor toxicities. Sci Immunol, 7(70):eabl3642.
[53]VelikkakamT, GollobKJ, DutraWO, 2022. Double-negative T cells: setting the stage for disease control or progression. Immunology, 165(4):371-385.
[54]VernaEC, PatelYA, AggarwalA, et al., 2020. Liver transplantation for hepatocellular carcinoma: management after the transplant. Am J Transplant, 20(2):333-347.
[55]VoelklS, MooreTV, RehliM, et al., 2009. Characterization of MHC class-I restricted TCRαβ+ CD4- CD8- double negative T cells recognizing the gp100 antigen from a melanoma patient after gp100 vaccination. Cancer Immunol Immunother, 58(5):709-718.
[56]XuH, ZhuXX, ChenJ, 2016. DNT cell inhibits the growth of pancreatic carcinoma via abnormal expressions of NKG2D and MICA in vivo. Biochem Biophys Res Commun, 469(2):145-150.
[57]XuX, LuD, LingQ, et al., 2016. Liver transplantation for hepatocellular carcinoma beyond the Milan criteria. Gut, 65(6):1035-1041.
[58]YangXY, LuD, WangR, et al., 2021. Single-cell profiling reveals distinct immune phenotypes that contribute to ischaemia-reperfusion injury after steatotic liver transplantation. Cell Prolif, 54(10):e13116.
[59]YaoFY, FerrellL, BassNM, et al., 2001. Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology, 33(6):1394-1403.
[60]YaoJL, LyD, DervovicD, et al., 2019. Human double negative T cells target lung cancer via ligand-dependent mechanisms that can be enhanced by IL-15. J Immunother Cancer, 7(1):17.
[61]YeQW, LingSB, ZhengSS, et al., 2019. Liquid biopsy in hepatocellular carcinoma: circulating tumor cells and circulating tumor DNA. Mol Cancer, 18:114.
[62]YoungKJ, YangLM, PhillipsMJ, et al., 2002. Donor-lymphocyte infusion induces transplantation tolerance by activating systemic and graft-infiltrating double-negative regulatory T cells. Blood, 100(9):3408-3414.
[63]YoungKJ, KayLS, PhillipsMJ, et al., 2003. Antitumor activity mediated by double-negative T cells. Cancer Res, 63(22):8014-8021.
[64]ZhangYJ, KongDR, WangH, 2020. Mucosal-associated invariant T cell in liver diseases. Int J Biol Sci, 16(3):460-470.
[65]ZhuoJY, SuRY, TanWY, et al., 2020. The ongoing trends of patient-derived xenograft models in oncology. Cancer Commun (Lond), 40(11):559-563.
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DOI:
10.1631/jzus.B2200528
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2023-05-15
Received:
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2023-05-16
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