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Research Progress of Different Subtypes of Myeloid-derived Suppressor Cells and Traditional Chinese Medicine Regulation Effect in Tumor Microenvironment
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 14, Pages: 45-54(2019)
- 作者机构：
1.上海中医药大学 基础医学院，经方理论应用研究中心，上海 201203；
2.上海交通大学 医学院 附属新华医院，上海 200092
- 作者简介：
- 基金信息：
DOI：10.13422/j.cnki.syfjx.20190626
CLC： R22; R242; R2-031; R285.5;R287Published：20 July 2019，
Published Online：04 December 2018，
Received：05 June 2018，
- 稿件说明：
扫 描 看 全 文
Zi-hang XU, Fei ZHANG, Yang-zhuang-zhuang ZHU, et al. Research Progress of Different Subtypes of Myeloid-derived Suppressor Cells and Traditional Chinese Medicine Regulation Effect in Tumor Microenvironment. [J]. Chinese Journal of Experimental Traditional Medical Formulae 25(14):45-54(2019)
Zi-hang XU, Fei ZHANG, Yang-zhuang-zhuang ZHU, et al. Research Progress of Different Subtypes of Myeloid-derived Suppressor Cells and Traditional Chinese Medicine Regulation Effect in Tumor Microenvironment. [J]. Chinese Journal of Experimental Traditional Medical Formulae 25(14):45-54(2019) DOI： 10.13422/j.cnki.syfjx.20190626.
摘要
肿瘤的诊疗手段不断提高，但是癌症的死亡率仍然是居高不下，目前学术界已意识到现有治疗思路的不足，逐渐将癌细胞“赶尽杀绝”的观念向与其“和平共处”转变，“带瘤生存”成为肿瘤学术界普遍接受的理念。肿瘤微环境是肿瘤细胞赖以生存和发展的场所，故调控肿瘤微环境，成为了肿瘤治疗的重要新策略。髓源抑制性细胞(MDSCs)是一群在肿瘤微环境中对T细胞具有免疫抑制特性的异质性细胞群体，在肿瘤免疫逃逸中发挥重要作用，如今以肿瘤微环境中的MDSCs为作用靶点亦为肿瘤治疗提供新思路。又由于MDSCs细胞亚群与嗜中性粒细胞及单核细胞的表型特征相似而主要可分为粒细胞样-髓源抑制性细胞(G-MDSCs)和单核细胞样-髓源抑制性细胞(M-MDSCs)两大亚型，但此2种亚型是如何区别于嗜中性粒细胞和单核细胞，不同亚型的MDSCs的功能特征又有何不一样，他们又是如何通过不同途径来累积、分化以及发挥免疫抑制作用，中医药素来擅长调控机体微环境，越来越多的研究显示中医复方及其活性成分能够有效抑制MDSCs的募集、扩增及活化，为中医药靶向肿瘤微环境中的MDSCs提供科学依据，但其具体通过何种途径调控何种亚型的MDSCs，目前尚缺乏较深入的机制探究。以往的文献综述的研究重点在MDSCs整体层面，该文将立足于MDSCs的具体亚型，并力求明确其生物学特性，以便在肿瘤微环境中实现更精确的靶向治疗。
Abstract
The diagnosis and treatment methods for cancer are being improved continually
but the mortality of cancer still remains high. At present
the academic circle has realized deficiency of existing treatment ideas
and the concept of cancer cells has been gradually changed from " extremely extinct" to " peaceful coexistence" . The concept of " survival with tumors" is universally accepted in the cancer academia. The tumor microenvironment is the place where tumor cells survive and develop. Therefore
regulation of the tumor microenvironment has become an important new strategy for tumor treatment. Myeloid-derived suppressor cells (MDSCs) are a group of heterogeneous cells that have immunosuppressive properties on T cells in the tumor microenvironment and play an important role in tumor immune escape. Now
therapy with MDSCs in the tumor microenvironment as the treatment targets also provides new ideas for the tumor treatment. As MDSCs subpopulations are similar with neutrophils and monocytes
they can be divided into two major subtypes: granulocyte-like myeloid-derived suppressor cells (G-MDSCs) and monocyte-myeloid-derived suppressor cells(M-MDSCs). But how to differ these two subtypes from neutrophils and monocytes. What are the differences in the functional characteristics of different subtypes of MDSCs. How do they accumulate
differentiate
and exert immunosuppressive effects through different pathways. Traditional Chinese medicine(TCM) has always been good at modulating the body's microenvironment. More and more researches have shown that
the recruitment
amplification and activation of MDSCs can be effectively inhibited by TCM compound and its active ingredients
providing scientific basis for Chinese medicine targeting MDSCs in the tumor microenvironment. However
which specific pathways could regulate G-MDSCs or M-MDSCs is still in need of further studies. Most previous literature focus on the overall level of MDSCs
while the this paper would be based on the specific subpopulations of MDSCs to clarify the biological characteristics of these two subtypes of MDSCs
so as to achieve more precise targeted therapy in the tumor microenvironment.
关键词
髓源抑制性细胞两大亚型肿瘤微环境中医药
Keywords
myeloid-derived suppressor cells (MDSCs)two subtypestumor microenvironmenttraditional Chinese medicine
references
Kuchuk O, Tuccitto A, Citterio D, et al. pH regulators to target the tumor immune microenvironment in human hepatocellular carcinoma [J].Onco Immunology, 2018, 7(7): e1445452.
邬晓东．运用中医药实现“带瘤生存”的体会[J]．新中医，2014，46(6)：235-236．
Böttcher J P, Bonavita E, Chakravarty P, et al. NK cells stimulate recruitment of cDC1 into the tumor microenvironment promoting cancer immune control [J].Cell, 2018, 172(5): 1022-1037, 1014.
Foucher E D, Ghigo C, Chouaib S, et al. Pancreatic ductal adenocarcinoma: a strong imbalance of good and bad immunological cops in the tumor microenvironment [J].Front Immunol, 2018, doi: 10.3389/fimmu.2018.01044http://doi.org/10.3389/fimmu.2018.01044.
SHAO L, ZHANG B, WANG L, et al. MMP-9-cleaved osteopontin isoform mediates tumor immune escape by inducing expansion of myeloid-derived suppressor cells [J].Biochem Biophys Res Commun, 2017, 493(4): 1478-1484.
Seo E H, Namgung J H, Oh C S, et al Association of chemokines and chemokine receptor expression with monocytic-myeloid-derived suppressor cells during tumor progression [J].Immune Netw, 2018, 18(3): e23.
李钦，胡继宏，高博，等．黄芪多糖在免疫调节方面的最新研究进展[J]．中国实验方剂学杂志，2017，23(2)：199-206．
朱元章，张贵彪，朱国福．中药复方抗肿瘤机制研究进展[J]．中国实验方剂学杂志，2017，23(16)：227-234．
刘蓓，韩凌斐．髓源性抑制细胞与促炎因子在卵巢恶性肿瘤中的研究进展[J]．国际妇产科学杂志，2018，45(1)：55-59．
王志宏，陈国江，彭晖．髓源性抑制细胞的生物学功能及其相关抑制剂的研究进展[J]．国际药学研究杂志，2018，45(1)：25-31．
Talmadge J E, Gabrilovich D I. History of myeloid-derived suppressor cells [J].Nat Rev Cancer, 2013, 13(10): 739-752.
Bronte V, Chappell D B, Apolloni E, et al. Unopposed production of granulocyte-macrophage colony-stimulating factor by tumors inhibits CD8t T cell responses by dysregulating antigen-presenting cell maturation [J].J Immunol, 1999, 162(10): 5728-5737.
Gabrilovich D, Ishida T, Oyama T, et al. Vascular endothelial growth factor inhibits the development of dendritic cells and dramatically affects the differentiation of multiple hematopoietic lineages in vivo [J].Blood, 1998, 92(11): 4150-4166.
Gabrilovich D I, Bronte V, Chen S H, et al. The terminology issue for myeloid-derived suppressor cells [J].Cancer Res, 2007, 67(1): 425.
Veglia F, Perego M, Gabrilovich D. Myeloid-derived suppressor cells coming of age [J].Nat Immunol, 2018, 19(2): 108.
Dolen Y, Gunaydin G, Esendagli G, et al. Granulocytic subset of myeloid derived suppressor cells in rats with mammary carcinoma [J].Cell Immunol, 2015, 295(1): 29-35.
Bronte V, Brandau S, CHEN S H, et al. Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards [J].Nat Commun, 2016, 7: 12150.
Strauss L, Sangaletti S, Consonni F M, et al. RORC1 regulates tumor-promoting ”Emergency” granulo-monocytopoiesis [J].Cancer Cell, 2015, 28(2): 253-269.
Pillay J, Tak T, Kamp V M, et al. Immune suppression by neutrophils and granulocytic myeloid-derived suppressor cells: similarities and differences [J].Cell Mol Life Sci, 2013, 70(20): 3813-3827.
Dumitru C A, Moses K, Trellakis S, et al. Neutrophils and granulocytic myeloid-derived suppressor cells: immunophenotyping, cell biology and clinical relevance in human oncology [J].Cancer Immunol Immunother, 2012, 61(8): 1155-1167.
Condamine T, Dominguez G, Youn J, et al. Lectin-type oxidized LDL receptor 1 distinguishes population of human polymorphonuclear myeloid-derived suppressor cells in cancer patients [J].Sci Immunol, 2016, 1(2): 8943.
Brandau S, Moses K, Lang S. The kinship of neutrophils and granulocytic myeloid-derived suppressor cells in cancer: cousins, siblings or twins? [J].Semin Cancer Biol, 2013, 23(3): 171-182.
Eruslanov E B, Singhal S, Albelda S M. Mouse versus human neutrophils in cancer: a major knowledge gap [J].Trends Cancer, 2017, 3(2): 149-160.
Schouppe E, Van O E, Laoui D, et al. Modulation of CD8(＋) T-cell activation events by monocytic and granulocytic myeloid-derived suppressor cells [J].Immunobiology, 2013, 218(11): 1385-1391.
Condamine T, Mastio J, Gabrilovich D I. Transcriptional regulation of myeloid-derived suppressor cells [J].J Leukoc Biol, 2015, 98(6): 913-922.
Tcyganov E, Mastio J, CHEN E, et al. Plasticity of myeloid-derived suppressor cells in cancer [J].Curr Opin Immunol, 2018, 51: 76-82.
Haverkamp J M, Smith A M, Weinlich R, et al. Myeloid-derived suppressor activity is mediated by monocytic lineages maintained by continuous inhibition of extrinsic and intrinsic death pathways [J].Immunity, 2014, 41(6): 947-959.
Casbon A J, Reynaud D, Park C, et al. Invasive breast cancer reprograms early myeloid differentiation in the bone marrow to generate immunosuppressive neutrophils [J].Proc Natl Acad Sci USA, 2015, 112(6): E566-575.
Ribechini E, Hutchinson J A, Hergovits S, et al. Novel GM-CSF signals via IFN-γR/IRF-1 and Akt/mTOR license monocytes for suppressor function [J].Blood Adv, 2017, 1(14): 947-960.
Youn J I, Kumar V, Collazo M, et al. Epigenetic silencing of retinoblastoma gene regulates pathologic differentiation of myeloid cells in cancer [J].Nat Immunol, 2013, 14(3): 211-220.
Pilatova K, Bencsikova B, Demlova R, et al. Myeloid-derived suppressor cells (MDSCs) in patients with solid tumors: considerations for granulocyte colony-stimulating factor treatment [J].Cancer Immunol Immunother, 2018(Suppl 1): 1-11.
Kumar V, CHENG P, Condamine T, et al. CD45 phosphatase regulates the fate of myeloid cells in tumor microenvironment by inhibiting STAT3 activity [J].Immunity, 2016, 196(Suppl 1): 303-315.
HUANG A, ZHANG B, WANG B, et al. Increased CD14(＋)HLA-DR (-/low) myeloid-derived suppressor cells correlate with extrathoracic metastasis and poor response to chemotherapy in non-small cell lung cancer patients [J].Cancer Immunol Immunother, 2013, 62(9): 1439-1451.
SUN H L, ZHOU X, XUE Y F, et al. Increased frequency and clinical signifcance of myeloid derived suppressor cells in human colorectal carcinoma [J].World J Gastroenterol, 2012, 18(25), 3303-3309.
ZHANG B, WANG Z, WU L, et al. Circulating and tumor-infiltrating myeloid-derived suppressor cells in patients with colorectal carcinoma [J].PLoS One, 2013, 8(2): e57114.
Diazmontero C M, Salem M L, Nishimura M I, et al. Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin-cyclophosphamide chemotherapy [J].Cancer Immunol Immunother, 2009, 58(1): 49-59.
YANG G, SHEN W, ZHANG Y, et al. Accumulation of myeloid-derived suppressor cells (MDSCs) induced by low levels of IL-6 correlates with poor prognosis in bladder cancer [J].Oncotarget, 2017, 8(24): 38378-38388.
Angell T E, Lechner M G, Smith A M, et al. Circulating myeloid-derived suppressor cells predict differentiated thyroid cancer diagnosis and extent [J].Tyroid, 2016, 26(3), 381-389.
Arihara F, Mizukoshi E, Kitahara M, et al. Increase in CD14＋HLA-DR-/low myeloid-derived suppressor cells in hepatocellular carcinoma patients and its impact on prognosis [J].Cancer Immunol Immunother, 2013, 62(8): 1421-1430.
Jordan K R, Amaria R N, Ramirez O, et al. Myeloid-derived suppressor cells are associated with disease progression and decreased overall survival in advanced-stage melanoma patients [J].Cancer Immunol Immunother, 2013, 62(11): 1711-1722.
ZHANG S, MA X, ZHU C, et al. The role of myeloid-derived suppressor cells in patients with solid tumors: a Meta-analysis [J].PLoS One, 2016, 11(10): e0164514.
WANG J, YANG J. Identification of CD4＋CD25＋CD127-regulatory T cells and CD14＋HLA-DR-/low myeloid-derived suppressor cells and their roles in the prognosis of breast cancer [J].Biomed Rep, 2016, 5(2): 208-212.
Kawano M, Mabuchi S, Matsumoto Y, et al. The significance of G-CSF expression and myeloid-derived suppressor cells in the chemoresistance of uterine cervical cancer [J].Sci Rep, 2015, 5(1): 18217.
Tada K, Kitano S, Shoji H, et al. Pretreatment immune status correlates with progression-free survival in chemotherapy-treated metastatic colorectal cancer patients [J].Cancer Immunol Res, 2016, 4(7): 592.
Romano A, Parrinello N L, Vetro C, et al. Circulating myeloid-derived suppressor cells correlate with clinical outcome in Hodgkin Lymphoma patients treated up-front with a risk-adapted strategy [J].Br J Haematol, 2015, 168(5): 689-700.
CHEN M F, KUAN F C, Yen T C, et al. IL-6-stimulated CD11b＋CD14＋HLA-DR－ myeloid-derived suppressor cells, are associated with progression and poor prognosis in squamous cell carcinoma of the esophagus [J].Oncotarget, 2014, 5(18): 8716-8728.
Lee S E, Lim J Y, Ryu D B, et al. Circulating immune cell phenotype can predict the outcome of lenalidomide plus low-dose dexamethasone treatment in patients with refractory/relapsed multiple myeloma [J].Cancer Immunol Immunother, 2016, 102(11): 1-12.
WANG D, AN G, XIE S, et al. The clinical and prognostic significance of CD14＋HLA-DR-/low myeloid-derived suppressor cells in hepatocellular carcinoma patients receiving radiotherapy [J].Tumour Biol, 2016, 37(8): 10427-10433.
Butterfield L H, ZHAO F, Lee S, et al. Immune correlates of GM-CSF and melanoma peptide vaccination in a randomized trial for the adjuvant therapy of resected high-risk melanoma (E4697) [J].Clin Cancer Res, 2017, 23(17): 5034.
Kimura T, Mckolanis J R, Dzubinski L A, et al. MUC1 vaccine for individuals with advanced adenoma of the colon: a cancer immunoprevention feasibility study [J].Cancer Prev Res (Phila), 2013, 6(1): 18-26.
De Coaña Y P, Wolodarski M, Poschke I, et al. Ipilimumab treatment decreases monocytic MDSCs and increases CD8 effector memory T cells in long-term survivors with advanced melanoma [J].Oncotarget, 2017, 8(13): 21539-21553.
Sade-Feldman M, Kanterman J, Klieger Y, et al. Clinical significance of circulating CD33＋CD11b＋HLA-DR-myeloid cells in Stage-Ⅳ melanoma patients treated with ipilimumab [J].Clinical Cancer Res, 2016, 22(23): 5661.
Martens A, Wistuba-Hamprecht K, Foppen M G, et al. Baseline peripheral blood biomarkers associated with clinical outcome of advanced melanoma patients treated with ipilimumab [J].Clinical Cancer Res, 2016, 22(12): 2908.
Casbon A J, Reynaud D, Park C, et al. Invasive breast cancer reprograms early myeloid differentiation in the bone marrow to generate immunosuppressive neutrophils [J].Proc Natl Acad Sci USA, 2015, 112(6): E566-575.
Condamine T, Kumar V, Ramachandran IR, et al. ER stress regulates myeloid-derived suppressor cell fate through TRAIL-R-mediated apoptosis [J].J Clin Invest, 2014, 124(6): 2626-2639.
QIN H, Lerman B, Sakamaki I, et al. Generation of a new therapeutic peptide that depletes myeloid-derived suppressor cells in tumor-bearing mice [J].Nat Med, 2014, 20(6): 676-681.
LU X, Horner J W, Paul E, et al. Effective combinatorial immunotherapy for castration-resistant prostate cancer [J].Nature, 2017, 543(7647): 728-732.
戴逸飞，戴丽，隋峰，等．苦寒中药及其活性成分抗肿瘤作用及机制研究进展[J]．中国实验方剂学杂志，2017，23(4)：215-221．
张建军，张永强，周芳，等．八珍汤加味调节大肠癌术后癌因性疲乏免疫功能[J]．中国实验方剂学杂志，2017，23(11)：196-201．
LIN W, LU J, CHEN B, et al. Progress in research on the effects of traditional Chinese medicine on the tumor microenvironment [J].J Integr Med, 2017, 15(4): 282-287.
Joyce J A, Fearon D T. T cell exclusion, immune privilege, and the tumor microenvironment [J].Science, 2015, 348(6230): 74-80.
刘丽萍，任翠爱，赵宏艳．甘草酸的免疫调节作用研究进展[J]．中国实验方剂学杂志，2010，16(6)：272-276．
Zci F, Sarsanov D, Erdogan Z I·, et al. Impact of personality traits, anxiety, depression and hopelessness level on quality of life in the patients with breast cancer [J].Eur J Breast Health, 2018, 14(2): 105-111.
何莉莎．疏肝健脾方对瘤前抑郁型乳腺癌MDSC-NKT细胞免疫重塑调控的研究[D]．北京：中国中医科学院，2014．
张玉人．扶正解郁方对抑郁障碍型乳腺癌所诱导的髓系抑制细胞的干预作用研究[D]．北京：北京中医药大学，2011．
魏华民．双参颗粒调控髓源性抑制细胞构筑肺转移前微环境的机制研究[D]．北京：中国中医科学院，2017．
徐扬．温阳通滞中药治疗晚期胃癌阳虚证疗效及对炎症免疫细胞因子、外周血髓源性抑制细胞、调节性T细胞水平的影响[J]．现代中西医结合杂志，2017，26(33)：3684-3686，3702．
LIN X, XU W, MENG S, et al. Shenling Baizhu San supresses colitis associated colorectal cancer through inhibition of epithelial-mesenchymal transition and myeloid-derived suppressor infiltration [J].BMC Complement Altern Med, 2015, 15(1): 126.
吴皓，李鸿，祁鑫，等．八宝丹对结肠癌荷瘤小鼠的血、脾和骨髓中的髓系抑制性细胞的影响[J]．中华中医药杂志，2014，29(2)：568-570．
孙晓润，陈苹苹，林悦，等．天然黄酮类化合物抗肿瘤作用靶点研究进展[J]．中国实验方剂学杂志，2017，23(6)：218-228．
焦延娜，韩淑燕．抗癌中药单体对肿瘤细胞自噬的调控[J]．中国实验方剂学杂志，2017，23(7)：206-214．
田新宇，范翠梅，渠田田，等．半枝莲总黄酮中7种成分的含量测定及抗肿瘤活性[J]．中国实验方剂学杂志，2017，23(1)：53-59．
吴端．体内外研究18β-甘草次酸对MDSC免疫抑制功能的影响[D]．厦门：厦门大学，2014．
彭美玉．信筒子醌治疗胰腺癌的作用和机制研究[D]．天津：天津医科大学，2014．
ZHOU J, WU J, CHEN X, et al. Icariin and its derivative, ICT, exert anti-inflammatory, anti-tumor effects, and modulate myeloid derived suppressive cells(MDSCs) funtions [J].Int Immunopharmacol, 2011, 11(7): 890-898.
柴旺，何小鹃，朱军璇，等．黄芪多糖对B16-F10荷瘤鼠髓样抑制细胞免疫活性的影响[J]．中国中医基础医学杂志，2012，18(1)：63-65．
Ouzounova M, Lee E, Piranlioglu R, et al. Monocytic and granulocytic myeloid derived suppressor cells differentially regulate spatiotemporal tumor plasticity during metastatic cascade [J].Nat Commun, 2017, doi: 10.1038/ncomms14979http://doi.org/10.1038/ncomms14979.
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