中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R

留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

肝癌微环境中肿瘤相关巨噬细胞的研究进展

汪鹏 仇建南 王忠夏 吴俊华 江春平

引用本文:
Citation:

肝癌微环境中肿瘤相关巨噬细胞的研究进展

DOI: 10.3969/j.issn.1001-5256.2023.05.033
基金项目: 

国家自然科学基金 (81572393)

利益冲突声明:本文不存在任何利益冲突。
作者贡献声明:汪鹏、仇建南负责收集数据,资料分析,撰写论文;王忠夏负责修改文章;江春平、吴俊华提供写作思路,指导撰写文章,修改文章并最后定稿。
详细信息
    通信作者:

    江春平,ChunpingJiang@126.com (ORCID: 0000-0001-8256-5731)

Research advances in tumor-associated macrophages in hepatocellular carcinoma microenvironment

Research funding: 

National Natural Science Foundation of China (81572393)

More Information
  • 摘要: 由于肝细胞癌早期临床症状不明显,患者确诊时大多已发展到晚期阶段。错失最佳手术机会的肝癌患者治疗手段有限,因此寻找新的治疗靶点变得十分重要。肿瘤相关巨噬细胞(TAM),是存在于肿瘤免疫微环境中一群巨噬细胞,影响着肝癌细胞的各种恶性行为和肿瘤内的免疫逃逸状态。介绍了TAM的起源和分类,归纳了TAM在肝癌血管增生、侵袭转移、干细胞特性的形成和维持、以及抗肿瘤免疫中的作用和机制,简述了当前针对TAM的治疗靶点的研究进展等,认为靶向TAM可能是一个有前景的临床治疗方向。

     

  • [1] LLOVET JM, KELLEY RK, VILLANUEVA A, et al. Hepatocellular carcinoma[J]. Nat Rev Dis Primers, 2021, 7(1): 6. DOI: 10.1038/s41572-020-00240-3.
    [2] FINN RS, RYOO BY, MERLE P, et al. Pembrolizumab as second-line therapy in patients with advanced hepatocellular carcinoma in KEYNOTE-240: A randomized, double-blind, phase Ⅲ trial[J]. J Clin Oncol, 2020, 38(3): 193-202. DOI: 10.1200/JCO.19.01307.
    [3] D'ALESSIO A, CAMMAROTA A, PRETE MG, et al. The evolving treatment paradigm of advanced hepatocellular carcinoma: putting all the pieces back together[J]. Curr Opin Oncol, 2021, 33(4): 386-394. DOI: 10.1097/CCO.0000000000000744.
    [4] PFISTER D, NÚÑEZ NG, PINYOL R, et al. NASH limits anti-tumour surveillance in immunotherapy-treated HCC[J]. Nature, 2021, 592(7854): 450-456. DOI: 10.1038/s41586-021-03362-0.
    [5] RITZ T, KRENKEL O, TACKE F. Dynamic plasticity of macrophage functions in diseased liver[J]. Cell Immunol, 2018, 330: 175-182. DOI: 10.1016/j.cellimm.2017.12.007.
    [6] SCHUPPAN D, SURABATTULA R, WANG XY. Determinants of fibrosis progression and regression in NASH[J]. J Hepatol, 2018, 68(2): 238-250. DOI: 10.1016/j.jhep.2017.11.012.
    [7] DEGROOTE H, van DIERENDONCK A, GEERTS A, et al. Preclinical and clinical therapeutic strategies affecting tumor-associated macrophages in hepatocellular carcinoma[J]. J Immunol Res, 2018, 2018: 7819520. DOI: 10.1155/2018/7819520.
    [8] CHEN DP, NING WR, JIANG ZZ, et al. Glycolytic activation of peritumoral monocytes fosters immune privilege via the PFKFB3-PD-L1 axis in human hepatocellular carcinoma[J]. J Hepatol, 2019, 71(2): 333-343. DOI: 10.1016/j.jhep.2019.04.007.
    [9] COMI M, AVANCINI D, SANTONI DE SIO F, et al. Coexpression of CD163 and CD141 identifies human circulating IL-10-producing dendritic cells (DC-10)[J]. Cell Mol Immunol, 2020, 17(1): 95-107. DOI: 10.1038/s41423-019-0218-0.
    [10] 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.
    [11] FUJITA N, NISHIE A, AISHIMA S, et al. Role of tumor-associated macrophages in the angiogenesis of well-differentiated hepatocellular carcinoma: pathological-radiological correlation[J]. Oncol Rep, 2014, 31(6): 2499-2505. DOI: 10.3892/or.2014.3138.
    [12] DONG S, GUO X, HAN F, et al. Emerging role of natural products in cancer immunotherapy[J]. Acta Pharm Sin B, 2022, 12(3): 1163-1185. DOI: 10.1016/j.apsb.2021.08.020.
    [13] LARIONOVA I, KAZAKOVA E, GERASHCHENKO T, et al. New angiogenic regulators produced by TAMs: Perspective for targeting tumor angiogenesis[J]. Cancers (Basel), 2021, 13(13): 3253. DOI: 10.3390/cancers13133253.
    [14] NAJAFI M, FARHOOD B, MORTEZAEE K. Extracellular matrix (ECM) stiffness and degradation as cancer drivers[J]. J Cell Biochem, 2019, 120(3): 2782-2790. DOI: 10.1002/jcb.27681.
    [15] BALKWILL FR, MANTOVANI A. Cancer-related inflammation: common themes and therapeutic opportunities[J]. Semin Cancer Biol, 2012, 22(1): 33-40. DOI: 10.1016/j.semcancer.2011.12.005.
    [16] JAKAB M, ROSTALSKI T, LEE KH, et al. Tie2 receptor in tumor-infiltrating macrophages is dispensable for tumor angiogenesis and tumor relapse after chemotherapy[J]. Cancer Res, 2022, 82(7): 1353-1364. DOI: 10.1158/0008-5472.CAN-21-3181.
    [17] BARTNECK M, SCHRAMMEN PL, MÖCKEL D, et al. The CCR2+ macrophage subset promotes pathogenic angiogenesis for tumor vascularization in fibrotic Livers[J]. Cell Mol Gastroenterol Hepatol, 2019, 7(2): 371-390. DOI: 10.1016/j.jcmgh.2018.10.007.
    [18] THOMANN S, WEILER S, WEI T, et al. YAP-induced Ccl2 expression is associated with a switch in hepatic macrophage identity and vascular remodelling in liver cancer[J]. Liver Int, 2021, 41(12): 3011-3023. DOI: 10.1111/liv.15048.
    [19] ZHANG J, CHANG L, ZHANG X, et al. Meta-analysis of the prognostic and clinical value of tumor-associated macrophages in hepatocellular carcinoma[J]. J Invest Surg, 2021, 34(3): 297-306. DOI: 10.1080/08941939.2019.1631411.
    [20] ZHU XD, ZHANG JB, ZHUANG PY, et al. High expression of macrophage colony-stimulating factor in peritumoral liver tissue is associated with poor survival after curative resection of hepatocellular carcinoma[J]. J Clin Oncol, 2008, 26(16): 2707-2716. DOI: 10.1200/jco.2007.15.6521.
    [21] LU Y, YANG A, QUAN C, et al. A single-cell atlas of the multicellular ecosystem of primary and metastatic hepatocellular carcinoma[J]. Nat Commun, 2022, 13(1): 4594. DOI: 10.1038/s41467-022-32283-3.
    [22] YAN L, XU F, DAI CL. Relationship between epithelial-to-mesenchymal transition and the inflammatory microenvironment of hepatocellular carcinoma[J]. J Exp Clin Cancer Res, 2018, 37(1): 203. DOI: 10.1186/s13046-018-0887-z.
    [23] YEUNG OW, LO CM, LING CC, et al. Alternatively activated (M2) macrophages promote tumour growth and invasiveness in hepatocellular carcinoma[J]. J Hepatol, 2015, 62(3): 607-616. DOI: 10.1016/j.jhep.2014.10.029.
    [24] ZHANG J, ZHANG Q, LOU Y, et al. Hypoxia-inducible factor-1α/interleukin-1β signaling enhances hepatoma epithelial-mesenchymal transition through macrophages in a hypoxic-inflammatory microenvironment[J]. Hepatology, 2018, 67(5): 1872-1889. DOI: 10.1002/hep.29681.
    [25] YANG HD, KIM HS, KIM SY, et al. HDAC6 suppresses Let-7i-5p to elicit TSP1/CD47-mediated anti-tumorigenesis and phagocytosis of hepatocellular carcinoma[J]. Hepatology, 2019, 70(4): 1262-1279. DOI: 10.1002/hep.30657.
    [26] FAN QM, JING YY, YU GF, et al. Tumor-associated macrophages promote cancer stem cell-like properties via transforming growth factor-beta1-induced epithelial-mesenchymal transition in hepatocellular carcinoma[J]. Cancer Lett, 2014, 352(2): 160-168. DOI: 10.1016/j.canlet.2014.05.008.
    [27] CHEN Y, WEN H, ZHOU C, et al. TNF-α derived from M2 tumor-associated macrophages promotes epithelial-mesenchymal transition and cancer stemness through the Wnt/β-catenin pathway in SMMC-7721 hepatocellular carcinoma cells[J]. Exp Cell Res, 2019, 378(1): 41-50. DOI: 10.1016/j.yexcr.2019.03.005.
    [28] WANG Y, WANG B, XIAO S, et al. miR-125a/b inhibits tumor-associated macrophages mediated in cancer stem cells of hepatocellular carcinoma by targeting CD90[J]. J Cell Biochem, 2019, 120(3): 3046-3055. DOI: 10.1002/jcb.27436.
    [29] WEI R, ZHU WW, YU GY, et al. S100 calcium-binding protein A9 from tumor-associated macrophage enhances cancer stem cell-like properties of hepatocellular carcinoma[J]. Int J Cancer, 2021, 148(5): 1233-1244. DOI: 10.1002/ijc.33371.
    [30] WAN S, ZHAO E, KRYCZEK I, et al. Tumor-associated macrophages produce interleukin 6 and signal via STAT3 to promote expansion of human hepatocellular carcinoma stem cells[J]. Gastroenterology, 2014, 147(6): 1393-1404. DOI: 10.1053/j.gastro.2014.08.039.
    [31] FU Y, LIU S, ZENG S, et al. From bench to bed: the tumor immune microenvironment and current immunotherapeutic strategies for hepatocellular carcinoma[J]. J Exp Clin Cancer Res, 2019, 38(1): 396. DOI: 10.1186/s13046-019-1396-4.
    [32] YANG L, ZHANG Y. Tumor-associated macrophages: from basic research to clinical application[J]. J Hematol Oncol, 2017, 10(1): 58. DOI: 10.1186/s13045-017-0430-2.
    [33] MA H, KANG Z, FOO TK, et al. Disrupted BRCA1-PALB2 interaction induces tumor immunosuppression and T-lymphocyte infiltration in HCC through cGAS-STING pathway[J]. Hepatology, 2023, 77(1): 33-47. DOI: 10.1002/hep.32335.
    [34] LIAO J, ZENG DN, LI JZ, et al. Type I IFNs repolarized a CD169+ macrophage population with anti-tumor potentials in hepatocellular carcinoma[J]. Mol Ther, 2022, 30(2): 632-643. DOI: 10.1016/j.ymthe.2021.09.021.
    [35] CHEW V, TOW C, TEO M, et al. Inflammatory tumour microenvironment is associated with superior survival in hepatocellular carcinoma patients[J]. J Hepatol, 2010, 52(3): 370-379. DOI: 10.1016/j.jhep.2009.07.013.
    [36] WANG H, KAUR G, SANKIN AI, et al. Immune checkpoint blockade and CAR-T cell therapy in hematologic malignancies[J]. J Hematol Oncol, 2019, 12(1): 59. DOI: 10.1186/s13045-019-0746-1.
    [37] LI H, WU K, TAO K, et al. Tim-3/galectin-9 signaling pathway mediates T-cell dysfunction and predicts poor prognosis in patients with hepatitis B virus-associated hepatocellular carcinoma[J]. Hepatology, 2012, 56(4): 1342-1351. DOI: 10.1002/hep.25777.
    [38] LOGTENBERG M, SCHEEREN FA, SCHUMACHER TN. The CD47-SIRPα immune checkpoint[J]. Immunity, 2020, 52(5): 742-752. DOI: 10.1016/j.immuni.2020.04.011.
    [39] MOLINIER-FRENKEL V, CASTELLANO F. Immunosuppressive enzymes in the tumor microenvironment[J]. FEBS Lett, 2017, 591(19): 3135-3157. DOI: 10.1002/1873-3468.12784.
    [40] ZHANG W, ZHU XD, SUN HC, et al. Depletion of tumor-associated macrophages enhances the effect of sorafenib in metastatic liver cancer models by antimetastatic and antiangiogenic effects[J]. Clin Cancer Res, 2010, 16(13): 3420-3430. DOI: 10.1158/1078-0432.CCR-09-2904.
    [41] SALMAN S, MEYERS DJ, WICKS EE, et al. HIF inhibitor 32-134D eradicates murine hepatocellular carcinoma in combination with anti-PD1 therapy[J]. J Clin Invest, 2022, 132(9). DOI: 10.1172/JCI156774.
    [42] LI G, LIU D, KIMCHI ET, et al. Nanoliposome C6-ceramide increases the anti-tumor immune response and slows growth of liver tumors in mice[J]. Gastroenterology, 2018, 154(4): 1024-1036. e9. DOI: 10.1053/j.gastro.2017.10.050.
    [43] AVILA MA, BERASAIN C. Targeting CCL2/CCR2 in tumor-infiltrating macrophages: A tool emerging out of the box against hepatocellular carcinoma[J]. Cell Mol Gastroenterol Hepatol, 2019, 7(2): 293-294. DOI: 10.1016/j.jcmgh.2018.11.002.
    [44] YAO W, BA Q, LI X, et al. A natural CCR2 antagonist relieves tumor-associated macrophage-mediated immunosuppression to produce a therapeutic effect for liver cancer[J]. EBioMedicine, 2017, 22: 58-67. DOI: 10.1016/j.ebiom.2017.07.014.
    [45] ZHU Y, YANG J, XU D, et al. Disruption of tumour-associated macrophage trafficking by the osteopontin-induced colony-stimulating factor-1 signalling sensitises hepatocellular carcinoma to anti-PD-L1 blockade[J]. Gut, 2019, 68(9): 1653-1666. DOI: 10.1136/gutjnl-2019-318419.
    [46] WEI CY, ZHU MX, ZHANG PF, et al. PKCα/ZFP64/CSF1 axis resets the tumor microenvironment and fuels anti-PD1 resistance in hepatocellular carcinoma[J]. J Hepatol, 2022, 77(1): 163-176. DOI: 10.1016/j.jhep.2022.02.019.
    [47] HUANG Y, GE W, ZHOU J, et al. The role of tumor associated macrophages in hepatocellular carcinoma[J]. J Cancer, 2021, 12(5): 1284-1294. DOI: 10.7150/jca.51346.
    [48] ARVANITAKIS K, KOLETSA T, MITROULIS I, et al. Tumor-associated macrophages in hepatocellular carcinoma pathogenesis, prognosis and therapy[J]. Cancers (Basel), 2022, 14(1): 226. DOI: 10.3390/cancers14010226.
    [49] YU Z, LI Y, LI Y, et al. Bufalin stimulates antitumor immune response by driving tumor-infiltrating macrophage toward M1 phenotype in hepatocellular carcinoma[J]. J Immunother Cancer, 2022, 10(5): e004297. DOI: 10.1136/jitc-2021-004297.
    [50] XIAO Z, CHUNG H, BANAN B, et al. Antibody mediated therapy targeting CD47 inhibits tumor progression of hepatocellular carcinoma[J]. Cancer Lett, 2015, 360(2): 302-309. DOI: 10.1016/j.canlet.2015.02.036.
  • 加载中
计量
  • 文章访问数:  505
  • HTML全文浏览量:  122
  • PDF下载量:  71
  • 被引次数: 0
出版历程
  • 收稿日期:  2022-08-29
  • 录用日期:  2022-10-13
  • 出版日期:  2023-05-20
  • 分享
  • 用微信扫码二维码

    分享至好友和朋友圈

目录

    /

    返回文章
    返回