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ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 37 Issue 6
Jun.  2021
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Article Navigation >  Journal of Clinical Hepatology  > 2021  >  37(6): 1473-1476

Influence of hepatocellular carcinoma microenvironment on myeloid-derived suppressor cells

DOI: 10.3969/j.issn.1001-5256.2021.06.053
  • 1.

    School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510000, China

  • 2.

    Department of TCM, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangdong Institute of Geriatrics, Guangzhou 510000, China

  • Received Date: 2020-11-17
  • Accepted Date: 2021-01-05
  • Published Date: 2021-06-20
    Abstract
  • Myeloid-derived suppressor cells (MDSCs) are a group of immature bone marrow cells with an immunosuppressive effect, and they are abundant in tumor patients and can induce tumor cells to escape the killing of immune cells and thus promote the development, progression, and metastasis of tumor. In recent years, its role in hepatocellular carcinoma microenvironment has attracted more and more attention, but the mechanisms of its recruitment and differentiation in hepatocellular carcinoma microenvironment have not been clearly elucidated. This article mainly summarizes the mechanism of action of tumor cells and tumor stromal cells in hepatocellular carcinoma microenvironment (such as hepatic stellate cells, tumor-associated fibroblasts, and tumor-associated endothelial cells) in the recruitment and differentiation of MDSCs, and it is proposed to target MDSCs as an adjuvant therapy to enhance the potential value of immunotherapy for liver cancer.

     

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    • References(37)
  • [1]
    SINGAL AG, LAMPERTICO P, NAHON P. Epidemiology and surveillance for hepatocellular carcinoma: New trends[J]. J Hepatol, 2020, 72(2): 250-261. DOI: 10.1016/j.jhep.2019.08.025.
    [2]
    HOECHST B, ORMANDY LA, BALLMAIER M, et al. A new population of myeloid-derived suppressor cells in hepatocellular carcinoma patients induces CD4(+)CD25(+)Foxp3(+) T cells[J]. Gastroenterology, 2008, 135(1): 234-243. DOI: 10.1053/j.gastro.2008.03.020.
    [3]
    IWATA T, KONDO Y, KIMURA O, et al. PD-L1+MDSCs are increased in HCC patients and induced by soluble factor in the tumor microenvironment[J]. Sci Rep, 2016, 6: 39296. DOI: 10.1038/srep39296.
    [4]
    ZHANG X, FU X, LI T, et al. The prognostic value of myeloid derived suppressor cell level in hepatocellular carcinoma: A systematic review and meta-analysis[J]. PLoS One, 2019, 14(12): e0225327. DOI: 10.1371/journal.pone.0225327.
    [5]
    TALMADGE JE, GABRILOVICH DI. History of myeloid-derived suppressor cells[J]. Nat Rev Cancer, 2013, 13(10): 739-752. DOI: 10.1038/nrc3581.
    [6]
    LU C, RONG D, ZHANG B, et al. Current perspectives on the immunosuppressive tumor microenvironment in hepatocellular carcinoma: Challenges and opportunities[J]. Mol Cancer, 2019, 18(1): 130. DOI: 10.1186/s12943-019-1047-6.
    [7]
    NAN J, XING YF, HU B, et al. Endoplasmic reticulum stress induced LOX-1+ CD15+ polymorphonuclear myeloid-derived suppressor cells in hepatocellular carcinoma[J]. Immunology, 2018, 154(1): 144-155. DOI: 10.1111/imm.12876.
    [8]
    WAN S, KUO N, KRYCZEK I, et al. Myeloid cells in hepatocellular carcinoma[J]. Hepatology, 2015, 62(4): 1304-1312. DOI: 10.1002/hep.27867.
    [9]
    VEGLIA F, PEREGO M, GABRILOVICH D. Myeloid-derived suppressor cells coming of age[J]. Nat Immunol, 2018, 19(2): 108-119. DOI: 10.1038/s41590-017-0022-x.
    [10]
    GIANNELLI G, RANI B, DITURI F, et al. Moving towards personalised therapy in patients with hepatocellular carcinoma: The role of the microenvironment[J]. Gut, 2014, 63(10): 1668-1676. DOI: 10.1136/gutjnl-2014-307323.
    [11]
    EGGERT T, WOLTER K, JI J, et al. Distinct functions of senescence-associated immune responses in liver tumor surveillance and tumor progression[J]. Cancer Cell, 2016, 30(4): 533-547. DOI: 10.1016/j.ccell.2016.09.003.
    [12]
    LI YM, LIU ZY, WANG JC, et al. Receptor-interacting protein kinase 3 deficiency recruits myeloid-derived suppressor cells to hepatocellular carcinoma through the chemokine (C-X-C Motif) ligand 1-chemokine (C-X-C Motif) receptor 2 axis[J]. Hepatology, 2019, 70(5): 1564-1581. DOI: 10.1002/hep.30676.
    [13]
    WANG D, LI X, LI J, et al. APOBEC3B interaction with PRC2 modulates microenvironment to promote HCC progression[J]. Gut, 2019, 68(10): 1846-1857. DOI: 10.1136/gutjnl-2018-317601.
    [14]
    SUN H, YANG W, TIAN Y, et al. An inflammatory-CCRK circuitry drives mTORC1-dependent metabolic and immunosuppressive reprogramming in obesity-associated hepatocellular carcinoma[J]. Nat Commun, 2018, 9(1): 5214. DOI: 10.1038/s41467-018-07402-8.
    [15]
    ZHOU J, LIU M, SUN H, et al. Hepatoma-intrinsic CCRK inhibition diminishes myeloid-derived suppressor cell immunosuppression and enhances immune-checkpoint blockade efficacy[J]. Gut, 2018, 67(5): 931-944. DOI: 10.1136/gutjnl-2017-314032.
    [16]
    ZENG X, ZHOU J, XIONG Z, et al. Cell cycle-related kinase reprograms the liver immune microenvironment to promote cancer metastasis[J]. Cell Mol Immunol, 2021, 18(4): 1005-1015. DOI: 10.1038/s41423-020-00534-2.
    [17]
    LIU LZ, ZHANG Z, ZHENG BH, et al. CCL15 recruits suppressive monocytes to facilitate immune escape and disease progression in hepatocellular carcinoma[J]. Hepatology, 2019, 69(1): 143-159. DOI: 10.1002/hep.30134.
    [18]
    LIN Y, YANG X, LIU W, et al. Chemerin has a protective role in hepatocellular carcinoma by inhibiting the expression of IL-6 and GM-CSF and MDSC accumulation[J]. Oncogene, 2017, 36(25): 3599-3608. DOI: 10.1038/onc.2016.516.
    [19]
    YANG X, YE X, ZHANG L, et al. Disruption of LTBP4 induced activated TGFβ1, immunosuppression signal and promoted pulmonary metastasis in hepatocellular carcinoma[J]. Onco Targets Ther, 2020, 13: 7007-7017. DOI: 10.2147/OTT.S246766.
    [20]
    LIU M, ZHOU J, LIU X, et al. Targeting monocyte-intrinsic enhancer reprogramming improves immunotherapy efficacy in hepatocellular carcinoma[J]. Gut, 2020, 69(2): 365-379. DOI: 10.1136/gutjnl-2018-317257.
    [21]
    HÖCHST B, SCHILDBERG FA, SAUERBORN P, et al. Activated human hepatic stellate cells induce myeloid derived suppressor cells from peripheral blood monocytes in a CD44-dependent fashion[J]. J Hepatol, 2013, 59(3): 528-535. DOI: 10.1016/j.jhep.2013.04.033.
    [22]
    CHOU HS, HSIEH CC, YANG HR, et al. Hepatic stellate cells regulate immune response by way of induction of myeloid suppressor cells in mice[J]. Hepatology, 2011, 53(3): 1007-1019. DOI: 10.1002/hep.24162.
    [23]
    HSIEH CC, HUNG CH, CHIANG M, et al. Hepatic stellate cells enhance liver cancer progression by inducing myeloid-derived suppressor cells through interleukin-6 signaling[J]. Int J Mol Sci, 2019, 20(20): 5079. DOI: 10.3390/ijms20205079.
    [24]
    XU Y, FANG F, JIAO H, et al. Activated hepatic stellate cells regulate MDSC migration through the SDF-1/CXCR4 axis in an orthotopic mouse model of hepatocellular carcinoma[J]. Cancer Immunol Immunother, 2019, 68(12): 1959-1969. DOI: 10.1007/s00262-019-02414-9.
    [25]
    XU Y, ZHAO W, XU J, et al. Activated hepatic stellate cells promote liver cancer by induction of myeloid-derived suppressor cells through cyclooxygenase-2[J]. Oncotarget, 2016, 7(8): 8866-8878. DOI: 10.18632/oncotarget.6839.
    [26]
    XU Y, HUANG Y, XU W, et al. Activated hepatic stellate cells (HSCs) exert immunosuppressive effects in hepatocellular carcinoma by producing complement C3[J]. Onco Targets Ther, 2020, 13: 1497-1505. DOI: 10.2147/OTT.S234920.
    [27]
    LI J, LI H, YU Y, et al. Mannan-binding lectin suppresses growth of hepatocellular carcinoma by regulating hepatic stellate cell activation via the ERK/COX-2/PGE2 pathway[J]. Oncoimmunology, 2019, 8(2): e1527650. DOI: 10.1080/2162402X.2018.1527650.
    [28]
    CHENG JT, DENG YN, YI HM, et al. Hepatic carcinoma-associated fibroblasts induce IDO-producing regulatory dendritic cells through IL-6-mediated STAT3 activation[J]. Oncogenesis, 2016, 5: e198. DOI: 10.1038/oncsis.2016.7.
    [29]
    DENG Y, CHENG J, FU B, et al. Hepatic carcinoma-associated fibroblasts enhance immune suppression by facilitating the generation of myeloid-derived suppressor cells[J]. Oncogene, 2017, 36(8): 1090-1101. DOI: 10.1038/onc.2016.273.
    [30]
    YIN Z, JIANG K, LI R, et al. Multipotent mesenchymal stromal cells play critical roles in hepatocellular carcinoma initiation, progression and therapy[J]. Mol Cancer, 2018, 17(1): 178. DOI: 10.1186/s12943-018-0926-6.
    [31]
    LACOTTE S, SLITS F, ORCI LA, et al. Impact of myeloid-derived suppressor cell on Kupffer cells from mouse livers with hepatocellular carcinoma[J]. Oncoimmunology, 2016, 5(11): e1234565. DOI: 10.1080/2162402X.2016.1234565.
    [32]
    HOECHST B, VOIGTLAENDER T, ORMANDY L, et al. Myeloid derived suppressor cells inhibit natural killer cells in patients with hepatocellular carcinoma via the NKp30 receptor[J]. Hepatology, 2009, 50(3): 799-807. DOI: 10.1002/hep.23054.
    [33]
    HU CE, GAN J, ZHANG RD, et al. Up-regulated myeloid-derived suppressor cell contributes to hepatocellular carcinoma development by impairing dendritic cell function[J]. Scand J Gastroenterol, 2011, 46(2): 156-164. DOI: 10.3109/00365521.2010.516450.
    [34]
    CHIU DK, TSE AP, XU IM, et al. Hypoxia inducible factor HIF-1 promotes myeloid-derived suppressor cells accumulation through ENTPD2/CD39L1 in hepatocellular carcinoma[J]. Nat Commun, 2017, 8(1): 517. DOI: 10.1038/s41467-017-00530-7.
    [35]
    CHIU DK, XU IM, LAI RK, et al. Hypoxia induces myeloid-derived suppressor cell recruitment to hepatocellular carcinoma through chemokine (C-C motif) ligand 26[J]. Hepatology, 2016, 64(3): 797-813. DOI: 10.1002/hep.28655.
    [36]
    YU SJ, MA C, HEINRICH B, et al. Targeting the crosstalk between cytokine-induced killer cells and myeloid-derived suppressor cells in hepatocellular carcinoma[J]. J Hepatol, 2019, 70(3): 449-457. DOI: 10.1016/j.jhep.2018.10.040.
    [37]
    WU H, LI SS, ZHOU M, et al. Palliative radiofrequency ablation accelerates the residual tumor progression through increasing tumor-infiltrating MDSCs and reducing T-Cell-mediated anti-tumor immune responses in animal model[J]. Front Oncol, 2020, 10: 1308. DOI: 10.3389/fonc.2020.01308.
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