药学学报, 2016, 51(10): 1513-1519
引用本文:
陈卉卉, 梁桂开, 姚张婷, 张洁琼, 陈羲, 丁玲. 巨噬细胞参与调控肿瘤化疗耐药性的研究进展[J]. 药学学报, 2016, 51(10): 1513-1519.
CHEN Hui-hui, LIANG Gui-kai, YAO Zhang-ting, ZHANG Jie-qiong, CHEN Xi, DING Ling. Advances in study of macrophages in chemotherapy resistance of cancer[J]. Acta Pharmaceutica Sinica, 2016, 51(10): 1513-1519.

巨噬细胞参与调控肿瘤化疗耐药性的研究进展
陈卉卉, 梁桂开, 姚张婷, 张洁琼, 陈羲, 丁玲
浙江大学药学院, 浙江 杭州 310058
摘要:
肿瘤相关巨噬细胞(tumor-associated macrophages,TAMs)是肿瘤微环境中极其重要的一类炎症细胞,能够分泌多种趋化因子和细胞因子,在肿瘤的发生、发展和转移中发挥重要的作用。近年来,越来越多的研究发现巨噬细胞会参与调控肿瘤化疗耐药,其分泌产生的化学物质会影响化疗药物的疗效。此外,一些化疗药物会影响巨噬细胞在肿瘤组织中的募集或生物学活性,进而影响其自身的抗肿瘤效应。本文就巨噬细胞在肿瘤化疗耐药中发挥的作用及其调控机制进行综述,并据此对靶向TAMs的临床治疗策略进行简单的概述。
关键词:    恶性肿瘤      巨噬细胞      化疗耐药     
Advances in study of macrophages in chemotherapy resistance of cancer
CHEN Hui-hui, LIANG Gui-kai, YAO Zhang-ting, ZHANG Jie-qiong, CHEN Xi, DING Ling
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
Abstract:
As extremely important inflammatory cells in the tumor microenvironment, tumor-associated macrophages (TAMs) can secrete a variety of chemokines and cytokines, which play an important role in the occurrence of tumor growth and metastasis. Recent years, increasing studies have shown that macrophages are associated with tumor chemotherapy sensitivity. The chemical substances produced by macrophages affect the efficacy of chemotherapeutic agents. In addition, some chemotherapeutic agents have an effect on the recruitment and bioactivity of macrophages in the tumor issue, which influences the anti-tumor efficacy of chemotherapy drugs. In this review, we summarize the roles of macrophages in the chemotherapy resistance, including the regulatory mechanism and the strategy of targeting macrophages.
Key words:    malignant tumor    macrophage    chemotherapy resistance   
收稿日期: 2016-04-25
DOI: 10.16438/j.0513-4870.2016-0393
基金项目: 国家自然科学基金面上项目(81473226).
通讯作者: 丁玲
Email: ld362@zju.edu.cn
相关功能
PDF(284KB) Free
打印本文
0
作者相关文章
陈卉卉  在本刊中的所有文章
梁桂开  在本刊中的所有文章
姚张婷  在本刊中的所有文章
张洁琼  在本刊中的所有文章
陈羲  在本刊中的所有文章
丁玲  在本刊中的所有文章

参考文献:
[1] Noy R,Pollard JW.Tumor-associated macrophages:from mechanisms to therapy[J].Immunity,2014,41:49-61.
[2] Zhang J,Yan Y,Yang Y,et al.High infiltration of tumorassociated macrophages influences poor prognosis in human gastric cancer patients,associates with the phenomenon of EMT[J].Medicine (Baltimore),2016,95:e2636.
[3] Chanmee T,Ontong P,Konno K,et al.Tumor-associated macrophages as major players in the tumor microenvironment[J].Cancers (Basel),2014,6:1670-1690.
[4] Pollard JW.Tumour-educated macrophages promote tumour progression and metastasis[J].Nat Rev Cancer,2004,4:71-78.
[5] De Palma M,Lewis CE.Macrophage regulation of tumor responses to anticancer therapies[J].Cancer Cell,2013,23:277-286.
[6] Ruffell B,Coussens LM.Macrophages and therapeutic resistance in cancer[J].Cancer Cell,2015,27:462-472.
[7] Mantovani A,Locati M.Tumor-associated macrophages as a paradigm of macrophage plasticity,diversity,and polarization:lessons and open questions[J].Arterioscler Thromb Vasc Biol,2013,33:1478-1483.
[8] Leblond MM,Gerault AN,Corroyer-Dulmont A,et al.Hypoxia induces macrophage polarization and re-education toward an M2 phenotype in U87 and U251 glioblastoma models[J].Oncoimmunology,2016,5:e1056442.
[9] Martinez FO,Helming L,Gordon S.Alternative activation of macrophages:an immunologic functional perspective[J].Annu Rev Immunol,2009,27:451-483.
[10] Zhang J,Cao J,Ma S,et al.Tumor hypoxia enhances non-small cell lung cancer metastasis by selectively promoting macrophage M2 polarization through the activation of ERK signaling[J].Oncotarget,2014,5:9664-9677.
[11] Movahedi K,Laoui D,Gysemans C,et al.Different tumor microenvironments contain functionally distinct subsets of macrophages derived from Ly6C (high) monocytes[J].Cancer Res,2010,70:5728-5739.
[12] Doedens AL,Stockmann C,Rubinstein MP,et al.Macrophage expression of hypoxia-inducible factor-1α suppresses T-cell function and promotes tumor progression[J].Cancer Res,2010,70:7465-7475.
[13] Chai CY,Chen WT,Hung WC,et al.Hypoxia-inducible factor-1α expression correlates with focal macrophage infiltration,angiogenesis and unfavourable prognosis in urothelial carcinoma[J].J Clin Pathol,2008,61:658-664.
[14] Riabov V,Gudima A,Wang N,et al.Role of tumor associated macrophages in tumor angiogenesis and lymphangiogenesis[J].Front Physiol,2014,5:75.
[15] Lin EY,Li JF,Bricard G,et al.Vascular endothelial growth factor restores delayed tumor progression in tumors depleted of macrophages[J].Mol Oncol,2007,1:288-302.
[16] Biswas SK,Gangi L,Paul S,et al.A distinct and unique transcriptional program expressed by tumor-associated macrophages (defective NF-κB and enhanced IRF-3/STAT1 activation)[J].Blood,2006,107:2112-2122.
[17] Liu J,Zhang N,Li Q,et al.Tumor-associated macrophages recruit CCR6+ regulatory T cells and promote the development of colorectal cancer via enhancing CCL20 production in mice[J].PLoS One,2011,6:e19495.
[18] Lin EY,Nguyen AV,Russell RG,et al.Colony-stimulating factor 1 promotes progression of mammary tumors to malignnancy[J].J Exp Med,2001,193:727-740.
[19] Ding L,Liang G,Yao Z,et al.Metformin prevents cancer metastasis by inhibiting M2-like polarization of tumor associated macrophages[J].Oncotarget,2015,6:36441-36455.
[20] Zheng Y,Cai Z,Wang S,et al.Macrophages are an abundant component of myeloma microenvironment and protect myeloma cells from chemotherapy drug-induced apoptosis[J].Blood,2009,114:3625-3628.
[21] Shree T,Olson OC,Elie BT,et al.Macrophages and cathepsin proteases blunt chemotherapeutic response in breast cancer[J].Genes Dev,2011,25:2465-2479.
[22] Ruan H,Hao S,Young P,et al.Targeting cathepsin B for cancer therapies[J].Horiz Cancer Res,2015,56:23-40.
[23] Bruchard M,Mignot G,Derangere V,et al.Chemotherapytriggered cathepsin B release in myeloid-derived suppressor cells activates the Nlrp3 inflammasome and promotes tumor growth[J].Nat Med,2013,19:57-64.
[24] Yang C,He L,He P,et al.Increased drug resistance in breast cancer by tumor-associated macrophages through IL-10/STAT3/bcl-2 signaling pathway[J].Med Oncol,2015,32:352.
[25] Weizman N,Krelin Y,Shabtay-Orbach A,et al.Macrophages mediate gemcitabine resistance of pancreatic adenocarcinoma by upregulating cytidine deaminase[J].Oncogene,2014,33:3812-3819.
[26] Angst E,Reber HA,Hines OJ,et al.Mononuclear cellderived interleukin-1β confers chemoresistance in pancreatic cancer cells by upregulation of cyclooxygenase-2[J].Surgery,2008,144:57-65.
[27] Paulus P,Stanley ER,Schafer R,et al.Colony-stimulating factor-1 antibody reverses chemoresistance in human MCF-7 breast cancer xenografts[J].Cancer Res,2006,66:4349-4356.
[28] Murdoch C,Muthana M,Coffelt SB,et al.The role of myeloid cells in the promotion of tumour angiogenesis[J].Nat Rev Cancer,2008,8:618-631.
[29] Lin L,Chen YS,Yao YD,et al.CCL18 from tumor-associated macrophages promotes angiogenesis in breast cancer[J].Oncotarget,2015,6:34758-34773.
[30] Stockmann C,Doedens A,Weidemann A,et al.Deletion of vascular endothelial growth factor in myeloid cells accelerates tumorigenesis[J].Nature,2008,456:814-818.
[31] Heldin CH,Rubin K,Pietras K,et al.High interstitial fluid pressure-an obstacle in cancer therapy[J].Nat Rev Cancer,2004,4:806-813.
[32] Tredan O,Galmarini CM,Patel K,et al.Drug resistance and the solid tumor microenvironment[J].J Natl Cancer Inst,2007,99:1441-1454.
[33] De Palma M,Naldini L.Angiopoietin-2 TIEs up macrophages in tumor angiogenesis[J].Clin Cancer Res,2011,17:5226-5232.
[34] He H,Xu J,Warren CM,et al.Endothelial cells provide an instructive niche for the differentiation and functional polarization of M2-like macrophages[J].Blood,2012,120:3152-3162.
[35] Brown JL,Cao ZA,Pinzon-Ortiz M,et al.A human monoclonal anti-ANG2 antibody leads to broad antitumor activity in combination with VEGF inhibitors and chemotherapy agents in preclinical models[J].Mol Cancer Ther,2010,9:145-156.
[36] Sinha P,Clements VK,Ostrand-Rosenberg S.Interleukin-13-regulated M2 macrophages in combination with myeloid suppressor cells block immune surveillance against metastasis[J].Cancer Res,2005,65:11743-11751.
[37] Wu A,Wei J,Kong LY,et al.Glioma cancer stem cells induce immunosuppressive macrophages/microglia[J].Neuro Oncol,2010,12:1113-1125.
[38] Ojalvo LS,King W,Cox D,et al.High-density gene expression analysis of tumor-associated macrophages from mouse mammary tumors[J].Am J Pathol,2009,174:1048-1064.
[39] Ruffell B,Chang-Strachan D,Chan V,et al.Macrophage IL-10 blocks CD8+T cell-dependent responses to chemotherapy by suppressing IL-12 expression in intratumoral dendritic cells[J].Cancer Cell,2014,26:623-637.
[40] Kryczek I,Zou L,Rodriguez P,et al.B7-H4 expression identifies a novel suppressive macrophage population in human ovarian carcinoma[J].J Exp Med,2006,203:871-881.
[41] Kuang DM,Zhao Q,Peng C,et al.Activated monocytes in peritumoral stroma of hepatocellular carcinoma foster immune privilege and disease progression through PD-L1[J].J Exp Med,2009,206:1327-1337.
[42] Goyne HE,Stone PJ,Burnett AF,et al.Ovarian tumor ascites CD14+ cells suppress dendritic cell-activated CD4+T-cell responses through IL-10 secretion and indoleamine 2,3-dioxygenase[J].J Immunother,2014,37:163-169.
[43] DeNardo DG,Brennan DJ,Rexhepaj E,et al.Leukocyte complexity predicts breast cancer survival and functionally regulates response to chemotherapy[J].Cancer Discov,2011,1:54-67.
[44] Mantovani A,Allavena P.The interaction of anticancer therapies with tumor-associated macrophages[J].J Exp Med,2015,212:435-445.
[45] Mitchem JB,Brennan DJ,Knolhoff BL,et al.Targeting tumor-infiltrating macrophages decreases tumor-initiating cells,relieves immunosuppression,and improves chemotherapeutic responses[J].Cancer Res,2013,73:1128-1141.
[46] Hughes R,Qian BZ,Rowan C,et al.Perivascular M2 macrophages stimulate tumor relapse after chemotherapy[J].Cancer Res,2015,75:3479-3491.
[47] Dijkgraaf EM,Heusinkveld M,Tummers B,et al.Chemotherapy alters monocyte differentiation to favor generation of cancer-supporting M2 macrophages in the tumor microenvironment[J].Cancer Res,2013,73:2480-2492.
[48] Cavnar MJ,Zeng S,Kim TS,et al.KIT oncogene inhibition drives intratumoral macrophage M2 polarization[J].J Exp Med,2013,210:2873-2886.
[49] Nakasone ES,Askautrud HA,Kees T,et al.Imaging tumorstroma interactions during chemotherapy reveals contributions of the microenvironment to resistance[J].Cancer Cell,2012,21:488-503.
[50] Mouchemore KA,Sampaio NG,Murrey MW,et al.Specific inhibition of PI3K p110δ inhibits CSF-1-induced macrophage spreading and invasive capacity[J].FEBS J,2013,280:5228-5236.
[51] Mok S,Koya RC,Tsui C,et al.Inhibition of CSF-1 receptor improves the antitumor efficacy of adoptive cell transfer immunotherapy[J].Cancer Res,2014,74:153-161.
[52] Rolny C,Mazzone M,Tugues S,et al.HRG inhibits tumor growth and metastasis by inducing macrophage polarization and vessel normalization through downregulation of PlGF[J].Cancer Cell,2011,19:31-44.
[53] Coscia M,Quaglino E,Iezzi M,et al.Zoledronic acid repolarizes tumour-associated macrophages and inhibits mammary carcinogenesis by targeting the mevalonate pathway[J].J Cell Mol Med,2010,14:2803-2815.