Advance Search
CAO Lingling, MEI Xiaocai, CHEN Qian, ZHANG Jian. Immunotherapy of γδ T cells in hepatocellular carcinoma: current status and perspectives[J]. Journal of Clinical Medicine in Practice, 2025, 29(7): 131-137. DOI: 10.7619/jcmp.20242075
Citation: CAO Lingling, MEI Xiaocai, CHEN Qian, ZHANG Jian. Immunotherapy of γδ T cells in hepatocellular carcinoma: current status and perspectives[J]. Journal of Clinical Medicine in Practice, 2025, 29(7): 131-137. DOI: 10.7619/jcmp.20242075
shu

Immunotherapy of γδ T cells in hepatocellular carcinoma: current status and perspectives

  • 1.

    Department of Hepatobiliary, Pancreatic and Spleen Surgery, the Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, 550000

  • 2.

    Department of Organ Transplantation, the Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550000

More Information
  • Received Date: May 16, 2024
  • Revised Date: August 27, 2024
    Graphical Abstract
    • Abstract

  • The hepatocellular carcinoma (HCC) poses a serious threat to human health. The main target of one of the immunotherapeutic approaches is γδ T cells. γδ T cells as one of the subpopulations of T lymphocytes can directly recognize and target HCC cells, making them a potential target for immunotherapy. In this paper, we discussed the biological properties of γδ T cells and their dual roles within HCC cells and therapeutic strategies, and provide an overview on the research of γδ T cell therapy for HCC.

    • FullText(HTML)
    • References (53)
  • [1]
    FOERSTER F, GAIRING S J, MÜLLER L, et al. NAFLD-driven HCC: Safety and efficacy of current and emerging treatment options[J]. J Hepatol, 2022, 76(2): 446-457. doi: 10.1016/j.jhep.2021.09.007
    [2]
    WANG Y, DENG B C. Hepatocellular carcinoma: molecular mechanism, targeted therapy, and biomarkers[J]. Cancer Metastasis Rev, 2023, 42(3): 629-652. doi: 10.1007/s10555-023-10084-4
    [3]
    CHEN Q, YANG S B, ZHANG Y W, et al. MiR-3682-3p directly targets FOXO3 and stimulates tumor stemness in hepatocellular carcinoma via a positive feedback loop involving FOXO3/PI3K/AKT/c-Myc[J]. World J Stem Cells, 2022, 14(7): 539-555. doi: 10.4252/wjsc.v14.i7.539
    [4]
    CHEN C, WANG Z H, DING Y, et al. Tumor microenvironment-mediated immune evasion in hepatocellular carcinoma[J]. Front Immunol, 2023, 14: 1133308. doi: 10.3389/fimmu.2023.1133308
    [5]
    PAPATHEODORIDI M, TAMPAKI M, LOK A S, et al. Risk of HBV reactivation during therapies for HCC: a systematic review[J]. Hepatology, 2022, 75(5): 1257-1274. doi: 10.1002/hep.32241
    [6]
    VITALE A, SVEGLIATI-BARONI G, ORTOLANI A, et al. Epidemiological trends and trajectories of MAFLD-associated hepatocellular carcinoma 2002-2033: the ITA. LI. CA database[J]. Gut, 2023, 72(1): 141-152. doi: 10.1136/gutjnl-2021-324915
    [7]
    CRANE H, GOFTON C, SHARMA A, et al. MAFLD: an optimal framework for understanding liver cancer phenotypes[J]. J Gastroenterol, 2023, 58(10): 947-964. doi: 10.1007/s00535-023-02021-7
    [8]
    NORERO B, DUFOUR J F. Should we undertake surveillance for HCC in patients with MAFLD?[J]. Ther Adv Endocrinol Metab, 2023, 14: 20420188231160389. doi: 10.1177/20420188231160389
    [9]
    LIU Y, XUN Z Z, MA K, et al. Identification of a tumour immune barrier in the HCC microenvironment that determines the efficacy of immunotherapy[J]. J Hepatol, 2023, 78(4): 770-782. doi: 10.1016/j.jhep.2023.01.011
    [10]
    CHENG K, CAI N, ZHU J H, et al. Tumor-associated macrophages in liver cancer: from mechanisms to therapy[J]. Cancer Commun, 2022, 42(11): 1112-1140. doi: 10.1002/cac2.12345
    [11]
    YOU M J, GAO Y N, FU J L, et al. Epigenetic regulation of HBV-specific tumor-infiltrating T cells in HBV-related HCC[J]. Hepatology, 2023, 78(3): 943-958. doi: 10.1097/HEP.0000000000000369
    [12]
    PAPADAKOS S P, ARVANITAKIS K, STERGIOU I E, et al. γδ T cells: a game changer in the future of hepatocellular carcinoma immunotherapy[J]. Int J Mol Sci, 2024, 25(3): 1381. doi: 10.3390/ijms25031381
    [13]
    HUNG Y P, SHAO Y Y, LEE J M, et al. Potential of circulating immune cells as biomarkers of nivolumab treatment efficacy for advanced hepatocellular carcinoma[J]. J Chin Med Assoc, 2021, 84(2): 144-150. doi: 10.1097/JCMA.0000000000000477
    [14]
    ZHANG L R, XU J L, ZHOU S Q, et al. Endothelial DGKG promotes tumor angiogenesis and immune evasion in hepatocellular carcinoma[J]. J Hepatol, 2024, 80(1): 82-98. doi: 10.1016/j.jhep.2023.10.006
    [15]
    YU H, SHI T Z, YAO L L, et al. Elevated nuclear PIGL disrupts the cMyc/BRD4 axis and improves PD-1 blockade therapy by dampening tumor immune evasion[J]. Cell Mol Immunol, 2023, 20(8): 867-880. doi: 10.1038/s41423-023-01048-3
    [16]
    HU Y, CHEN D, HONG M J, et al. Apoptosis, pyroptosis, and ferroptosis conspiringly induce immunosuppressive hepatocellular carcinoma microenvironment and γδ T-cell imbalance[J]. Front Immunol, 2022, 13: 845974. doi: 10.3389/fimmu.2022.845974
    [17]
    YI Y, HE H W, WANG J X, et al. The functional impairment of HCC-infiltrating γδ T cells, partially mediated by regulatory T cells in a TGFβ- and IL-10-dependent manner[J]. J Hepatol, 2013, 58(5): 977-983. doi: 10.1016/j.jhep.2012.12.015
    [18]
    HE W J, HU Y, CHEN D, et al. Hepatocellular carcinoma-infiltrating γδ T cells are functionally defected and allogenic Vδ2+ γδ T cell can be a promising complement[J]. Clin Transl Med, 2022, 12(4): e800. doi: 10.1002/ctm2.800
    [19]
    HAN J W, YOON S K. Tissue-resident lymphocytes: implications in immunotherapy for hepatocellular carcinoma[J]. Int J Mol Sci, 2020, 22(1): 232. doi: 10.3390/ijms22010232
    [20]
    VANTOUROUT P, LAING A, WOODWARD M J, et al. Heteromeric interactions regulate butyrophilin (BTN) and BTN-like molecules governing γδ T cell biology[J]. Proc Natl Acad Sci U S A, 2018, 115(5): 1039-1044. doi: 10.1073/pnas.1701237115
    [21]
    HERRMANN T, FICHTNER A S, KARUNAKARAN M M. An update on the molecular basis of phosphoantigen recognition by Vγ9Vδ2 T cells[J]. Cells, 2020, 9(6): 1433. doi: 10.3390/cells9061433
    [22]
    MA L, FENG Y M, ZHOU Z S. A close look at current γδ T-cell immunotherapy[J]. Front Immunol, 2023, 14: 1140623. doi: 10.3389/fimmu.2023.1140623
    [23]
    CHEN D, GUO Y L, JIANG J H, et al. γδ T cell exhaustion: Opportunities for intervention[J]. J Leukoc Biol, 2022, 112(6): 1669-1676. doi: 10.1002/JLB.5MR0722-777R
    [24]
    佟佳益, 郑改改, 王宇, 等. 医学人工智能研究热点双聚类分析[J]. 实用临床医药杂志, 2024, 28(3): 13-17, 22. doi: 10.7619/jcmp.20232042
    [25]
    SEBESTYEN Z, PRINZ I, DÉCHANET-MERVILLE J, et al. Translating gammadelta (γδ) T cells and their receptors into cancer cell therapies[J]. Nat Rev Drug Discov, 2020, 19(3): 169-184. doi: 10.1038/s41573-019-0038-z
    [26]
    DEKKERS J F, ALIEVA M, CLEVEN A, et al. Uncovering the mode of action of engineered T cells in patient cancer organoids[J]. Nat Biotechnol, 2023, 41(1): 60-69. doi: 10.1038/s41587-022-01397-w
    [27]
    ZAKERI N, HALL A, SWADLING L, et al. Characterisation and induction of tissue-resident gamma delta T-cells to target hepatocellular carcinoma[J]. Nat Commun, 2022, 13(1): 1372. doi: 10.1038/s41467-022-29012-1
    [28]
    MCGRAW J M, THELEN F, HAMPTON E N, et al. JAML promotes CD8 and γδ T cell antitumor immunity and is a novel target for cancer immunotherapy[J]. J Exp Med, 2021, 218(10): e20202644. doi: 10.1084/jem.20202644
    [29]
    TITOV A, ZMIEVSKAYA E, GANEEVA I, et al. Adoptive immunotherapy beyond CAR T-cells[J]. Cancers, 2021, 13(4): 743. doi: 10.3390/cancers13040743
    [30]
    TOSOLINI M, PONT F, POUPOT M, et al. Assessment of tumor-infiltrating TCRV γ 9V δ 2 γδ lymphocyte abundance by deconvolution of human cancers microarrays[J]. Oncoimmunology, 2017, 6(3): e1284723. doi: 10.1080/2162402X.2017.1284723
    [31]
    GENTLES A J, NEWMAN A M, LIU C L, et al. The prognostic landscape of genes and infiltrating immune cells across human cancers[J]. Nat Med, 2015, 21(8): 938-945. doi: 10.1038/nm.3909
    [32]
    ZHAO N, DANG H, MA L C, et al. Intratumoral γδ T-cell infiltrates, chemokine (C-C motif) ligand 4/chemokine (C-C motif) ligand 5 protein expression and survival in patients with hepatocellular carcinoma[J]. Hepatology, 2021, 73(3): 1045-1060. doi: 10.1002/hep.31412
    [33]
    DE VRIES N L, VAN DE HAAR J, VENINGA V, et al. γδ T cells are effectors of immunotherapy in cancers with HLA class I defects[J]. Nature, 2023, 613(7945): 743-750. doi: 10.1038/s41586-022-05593-1
    [34]
    DU Y Y, PENG Q W, CHENG D, et al. Cancer cell-expressed BTNL2 facilitates tumour immune escape via engagement with IL-17A-producing γδ T cells[J]. Nat Commun, 2022, 13(1): 231. doi: 10.1038/s41467-021-27936-8
    [35]
    JIANG H, YANG Z, SONG Z Y, et al. γδ T cells in hepatocellular carcinoma patients present cytotoxic activity but are reduced in potency due to IL-2 and IL-21 pathways[J]. Int Immunopharmacol, 2019, 70: 167-173. doi: 10.1016/j.intimp.2019.02.019
    [36]
    WANG X, TIAN Z. γδ T cells in liver diseases[J]. Front Med, 2018, 12(3): 262-268. doi: 10.1007/s11684-017-0584-x
    [37]
    KANG I, KIM Y, LEE H K. γδ T cells as a potential therapeutic agent for glioblastoma[J]. Front Immunol, 2023, 14: 1273986. doi: 10.3389/fimmu.2023.1273986
    [38]
    XIAO Z Q, WANG S S, TIAN Y X, et al. METTL3-mediated m6A methylation orchestrates mRNA stability and dsRNA contents to equilibrate γδ T1 and γδ T17 cells[J]. Cell Rep, 2023, 42(7): 112684. doi: 10.1016/j.celrep.2023.112684
    [39]
    YUAN L J, MA X Q, YANG Y Y, et al. Phosphoantigens glue butyrophilin 3A1 and 2A1 to activate Vγ9Vδ2 T cells[J]. Nature, 2023, 621(7980): 840-848. doi: 10.1038/s41586-023-06525-3
    [40]
    SILVA-SANTOS B, MENSURADO S, COFFELT S B. γδ T cells: pleiotropic immune effectors with therapeutic potential in cancer[J]. Nat Rev Cancer, 2019, 19(7): 392-404. doi: 10.1038/s41568-019-0153-5
    [41]
    SONG M J, HE J Y, PAN Q Z, et al. Cancer-associated fibroblast-mediated cellular crosstalk supports hepatocellular carcinoma progression[J]. Hepatology, 2021, 73(5): 1717-1735. doi: 10.1002/hep.31792
    [42]
    HAN S L, BAO X Y, ZOU Y F, et al. D-lactate modulates M2 tumor-associated macrophages and remodels immunosuppressive tumor microenvironment for hepatocellular carcinoma[J]. Sci Adv, 2023, 9(29): eadg2697. doi: 10.1126/sciadv.adg2697
    [43]
    TOUTIRAIS O, CHARTIER P, DUBOIS D, et al. Constitutive expression of TGF-bêta1, interleukin-6 and interleukin-8 by tumor cells as a major component of immune escape in human ovarian carcinoma[J]. Eur Cytokine Netw, 2003, 14(4): 246-255.
    [44]
    CHOI H, LEE Y, PARK S A, et al. Human allogenic γδ T cells kill patient-derived glioblastoma cells expressing high levels of DNAM-1 ligands[J]. Oncoimmunology, 2022, 11(1): 2138152. doi: 10.1080/2162402X.2022.2138152
    [45]
    MONDRAGÓN L, KROEMER G, GALLUZZI L. Immunosuppressive γδ T cells foster pancreatic carcinogenesis[J]. Oncoimmunology, 2016, 5(11): e1237328. doi: 10.1080/2162402X.2016.1237328
    [46]
    MAKKOUK A, YANG X C, BARCA T, et al. Off-the-shelf Vδ1 gamma delta T cells engineered with glypican-3 (GPC-3)-specific chimeric antigen receptor (CAR) and soluble IL-15 display robust antitumor efficacy against hepatocellular carcinoma[J]. J Immunother Cancer, 2021, 9(12): e003441. doi: 10.1136/jitc-2021-003441
    [47]
    CAO W Q, SHARMA M, IMAM R, et al. Study on diagnostic values of astrocyte elevated gene 1 (AEG-1) and glypican 3 (GPC-3) in hepatocellular carcinoma[J]. Am J Clin Pathol, 2019, 152(5): 647-655. doi: 10.1093/ajcp/aqz086
    [48]
    DANGI A, HUSAIN I, JORDAN C Z, et al. Blocking CCL8-CCR8-mediated early allograft inflammation improves kidney transplant function[J]. J Am Soc Nephrol, 2022, 33(10): 1876-1890. doi: 10.1681/ASN.2022020139
    [49]
    WEI Y, LAO X M, XIAO X, et al. Plasma cell polarization to the immunoglobulin G phenotype in hepatocellular carcinomas involves epigenetic alterations and promotes hepatoma progression in mice[J]. Gastroenterology, 2019, 156(6): 1890-1904. e16. doi: 10.1053/j.gastro.2019.01.250
    [50]
    LIANG J Y, WANG D S, LIN H C, et al. A novel ferroptosis-related gene signature for overall survival prediction in patients with hepatocellular carcinoma[J]. Int J Biol Sci, 2020, 16(13): 2430-2441. doi: 10.7150/ijbs.45050
    [51]
    GUO M Z, YUAN F F, QI F, et al. Expression and clinical significance of LAG-3, FGL1, PD-L1 and CD8+T cells in hepatocellular carcinoma using multiplex quantitative analysis[J]. J Transl Med, 2020, 18(1): 306. doi: 10.1186/s12967-020-02469-8
    [52]
    SCHULZ-JUERGENSEN S, MARISCHEN L, WESCH D, et al. Markers of operational immune tolerance after pediatric liver transplantation in patients under immunosuppression[J]. Pediatr Transplant, 2013, 17(4): 348-354. doi: 10.1111/petr.12079
    [53]
    ZHANG R Y, ZHANG Z, LIU Z K, et al. Adoptive cell transfer therapy for hepatocellular carcinoma[J]. Front Med, 2019, 13(1): 3-11. doi: 10.1007/s11684-019-0684-x
    • Related Articles

  • Related Articles

    [1]WANG Xinzi, QIU Yibo, DENG Yu, YU Siming. Research progress of treatment of vascular calcification in patients with maintenance hemodialysis[J]. Journal of Clinical Medicine in Practice, 2022, 26(22): 144-148. DOI: 10.7619/jcmp.20221784
    [2]WU Guangbiao. Effect of hemodialysis combined with hemoperfusion in the treatment of patients with chronic kidney disease-mineral and bone disorder[J]. Journal of Clinical Medicine in Practice, 2020, 24(10): 110-112. DOI: 10.7619/jcmp.202010028
    [3]GU Jing, ZHAN GHui. Effects of high-flux hemodialysis combined with alprostadil in treating chronic renal failure[J]. Journal of Clinical Medicine in Practice, 2019, (1): 85-88,92. DOI: 10.7619/jcmp.201901023
    [4]ZHANG Ying. Effect of predictive nursing in prevention of noscomial infection in diabetic nephropathy patients with hemodialysis[J]. Journal of Clinical Medicine in Practice, 2018, (6): 36-39. DOI: 10.7619/jcmp.201806011
    [5]HE Pinghong, JIANG Wenyong, SU Fengxian, HU Shanshan, DA Jingjing, ZHA Yan. Clinical effect of high flux hemodialysis foRAECOPD patients complicated with renal insufficiency[J]. Journal of Clinical Medicine in Practice, 2017, (9): 24-27. DOI: 10.7619/jcmp.201709006
    [6]MIAO Changxian, XIE Xianmin, CONG Zhihua. Influence of low calcium dialysate calcium on calcium and phosphorus metabolism and parathyroid hormone in patients with maintenance hemodialysis[J]. Journal of Clinical Medicine in Practice, 2017, (3): 29-31. DOI: 10.7619/jcmp.201703009
    [7]TANG Yumei, XU Jixian, LI Gang, WANG Yuan. Influence of high flux hemodialysis on serum β2-microglobulin and parathyroid hormone[J]. Journal of Clinical Medicine in Practice, 2015, (7): 74-76. DOI: 10.7619/jcmp.201507021
    [8]Comparison between on-line hemodiafiltration and high-flux hemodialysis for middle-molecule solues removal[J]. Journal of Clinical Medicine in Practice, 2014, (19): 182-184. DOI: 10.7619/jcmp.201419063
    [9]TANG Xiaojun. Related risk factors of cognitive dysfunction in patients with maintenance hemodialysis[J]. Journal of Clinical Medicine in Practice, 2014, (15): 158-159,162. DOI: 10.7619/jcmp.201415055
    [10]YANG Biyu. Preventive effect of nursing intervention on hypoglycemia of hemodialysis in diabetic nephropathy patients[J]. Journal of Clinical Medicine in Practice, 2014, (12): 8-10. DOI: 10.7619/jcmp.201412003

Catalog

    Get Citation
    PDF
    XML
    Article views (36) PDF downloads (8) Cited by()
    Turn off MathJax
    Article Contents
    Abstract
    References
    Related Articles

    © 2020 《实用临床医药杂志》编辑部

    Address: 江苏省扬州市江阳中路136号，扬州大学江阳路北校区14号楼201室China Pos: 225009Tel: 0514-87978917、87978989、87978807

    苏公网安备 32100302010246号

    Supported by: Beijing Renhe Information Technology Co., Ltd.   Baidu Analytics

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return