References:

<HIDE>

[1]Amin MB, Greene FL, Edge SB, et al., 2017. The eighth edition AJCC cancer staging manual: continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. CA Cancer J Clin, 67(2):93-99.

[2]Baer C, Squadrito ML, Laoui D, et al., 2016. Suppression of microRNA activity amplifies IFN-γ-induced macrophage activation and promotes anti-tumour immunity. Nat Cell Biol, 18(7):790-802.

[3]Bai XZ, Zhang JL, Cao MY, et al., 2018. MicroRNA-146a protects against LPS-induced organ damage by inhibiting Notch1 in macrophage. Int Immunopharmacol, 63:220-226.

[4]Bala S, Marcos M, Kodys K, et al., 2011. Up-regulation of microRNA-155 in macrophages contributes to increased tumor necrosis factor α (TNFα) production via increased mRNA half-life in alcoholic liver disease. J Biol Chem, 286(2):1436-1444.

[5]Banerjee S, Xie N, Cui HC, et al., 2013a. MicroRNA let-7c regulates macrophage polarization. J Immunol, 190(12):6542-6549.

[6]Banerjee S, Cui HC, Xie N, et al., 2013b. miR-125a-5p regulates differential activation of macrophages and inflammation. J Biol Chem, 288(49):35428-35436.

[7]Batool A, Wang YQ, Hao XX, et al., 2018. A miR-125b/ CSF1-CX3CL1/tumor-associated macrophage recruitment axis controls testicular germ cell tumor growth. Cell Death Dis, 9(10):962.

[8]Binenbaum Y, Fridman E, Yaari Z, et al., 2018. Transfer of miRNA in macrophage-derived exosomes induces drug resistance in pancreatic adenocarcinoma. Cancer Res, 78(18):5287-5299.

[9]Boldin MP, Taganov KD, Rao DS, et al., 2011. miR-146a is a significant brake on autoimmunity, myeloproliferation, and cancer in mice. J Exp Med, 208(6):1189-1201.

[10]Chafin CB, Regna NL, Caudell DL, et al., 2014. MicroRNA-let-7a promotes E2F-mediated cell proliferation and NFκB activation in vitro. Cell Mol Immunol, 11(1):79-83.

[11]Chai ZT, Zhu XD, Ao JY, et al., 2015. MicroRNA-26a suppresses recruitment of macrophages by down-regulating macrophage colony-stimulating factor expression through the PI3K/Akt pathway in hepatocellular carcinoma. J Hematol Oncol, 8:56.

[12]Challagundla KB, Wise PM, Neviani P, et al., 2015. Exosome-mediated transfer of microRNAs within the tumor microenvironment and neuroblastoma resistance to chemotherapy. J Natl Cancer Inst, 107(7):djv135.

[13]Chaudhuri AA, So AYL, Sinha N, et al., 2011. MicroRNA-125b potentiates macrophage activation. J Immunol, 187(10):5062-5068.

[14]Chen X, Ying X, Wang XJ, et al., 2017. Exosomes derived from hypoxic epithelial ovarian cancer deliver microRNA-940 to induce macrophage M2 polarization. Oncol Rep, 38(1):522-528.

[15]Chen Y, Wang SX, Mu R, et al., 2014. Dysregulation of the miR-324-5p-CUEDC2 axis leads to macrophage dysfunction and is associated with colon cancer. Cell Rep, 7(6):1982-1993.

[16]Cooks T, Pateras IS, Jenkins LM, et al., 2018. Mutant p53 cancers reprogram macrophages to tumor supporting macrophages via exosomal miR-1246. Nat Commun, 9(1):771.

[17]Cortez-Retamozo V, Etzrodt M, Newton A, et al., 2012. Origins of tumor-associated macrophages and neutrophils. Proc Natl Acad Sci USA, 109(7):2491-2496.

[18]Curtale G, 2018. MiRNAs at the crossroads between innate immunity and cancer: focus on macrophages. Cells, 7(2):12.

[19]Curtale G, Mirolo M, Renzi TA, et al., 2013. Negative regulation of Toll-like receptor 4 signaling by IL-10-dependent microRNA-146b. Proc Natl Acad Sci USA, 110(28):11499-11504.

[20]Dean M, Fojo T, Bates S, 2005. Tumour stem cells and drug resistance. Nat Rev Cancer, 5(4):275-284.

[21]el Andaloussi S, Mäger I, Breakefield XO, et al., 2013. Extracellular vesicles: biology and emerging therapeutic opportunities. Nat Rev Drug Discov, 12(5):347-357.

[22]el Gazzar M, Church A, Liu TF, et al., 2011. MicroRNA-146a regulates both transcription silencing and translation disruption of TNF-α during TLR4-induced gene reprogramming. J Leukoc Biol, 90(3):509-519.

[23]Etzrodt M, Cortez-Retamozo V, Newton A, et al., 2012. Regulation of monocyte functional heterogeneity by miR-146a and Relb. Cell Rep, 1(4):317-324.

[24]Fabbri M, Paone A, Calore F, et al., 2012. MicroRNAs bind to Toll-like receptors to induce prometastatic inflammatory response. Proc Natl Acad Sci USA, 109(31):E2110-E2116.

[25]Fortunato O, Borzi C, Milione M, et al., 2019. Circulating miR-320a promotes immunosuppressive macrophages M2 phenotype associated with lung cancer risk. Int J Cancer, 144(11):2746-2761.

[26]Frank AC, Ebersberger S, Fink AF, et al., 2019. Apoptotic tumor cell-derived microRNA-375 uses CD36 to alter the tumor-associated macrophage phenotype. Nat Commun, 10(1):1135.

[27]Franklin RA, Liao W, Sarkar A, et al., 2014. The cellular and molecular origin of tumor-associated macrophages. Science, 344(6186):921-925.

[28]Funahashi Y, Kato N, Masuda T, et al., 2019. miR-146a targeted to splenic macrophages prevents sepsis-induced multiple organ injury. Lab Invest, 99(8):1130-1142.

[29]Geissmann F, Manz MG, Jung S, et al., 2010. Development of monocytes, macrophages, and dendritic cells. Science, 327(5966):656-661.

[30]Ghani S, Riemke P, Schönheit J, et al., 2011. Macrophage development from HSCs requires PU.1-coordinated microRNA expression. Blood, 118(8):2275-2284.

[31]Guerriero JL, 2018. Macrophages: the road less traveled, changing anticancer therapy. Trends Mol Med, 24(5):472-489.

[32]Guo J, Liu C, Wang W, et al., 2018. Identification of serum miR-1915-3p and miR-455-3p as biomarkers for breast cancer. PLoS ONE, 13(7):e0200716.

[33]Ha MJ, Kim VN, 2014. Regulation of microRNA biogenesis. Nat Rev Mol Cell Biol, 15(8):509-524.

[34]He M, Xu ZQ, Ding T, et al., 2009. MicroRNA-155 regulates inflammatory cytokine production in tumor-associated macrophages via targeting C/EBPβ. Cell Mol Immunol, 6(5):343-352.

[35]Hsieh CH, Tai SK, Yang MH, 2018. Snail-overexpressing cancer cells promote M2-like polarization of tumor-associated macrophages by delivering miR-21-abundant exosomes. Neoplasia, 20(8):775-788.

[36]Hsu YL, Hung JY, Chang WA, et al., 2018. Hypoxic lung-cancer-derived extracellular vesicle microRNA-103a increases the oncogenic effects of macrophages by targeting PTEN. Mol Ther, 26(2):568-581.

[37]Huang F, Zhao JL, Wang L, et al., 2017. miR-148a-3p mediates notch signaling to promote the differentiation and M1 activation of macrophages. Front Immunol, 8:1327.

[38]Ismail N, Wang YJ, Dakhlallah D, et al., 2013. Macrophage microvesicles induce macrophage differentiation and miR-223 transfer. Blood, 121(6):984-995.

[39]Jang JY, Lee JK, Jeon YK, et al., 2013. Exosome derived from epigallocatechin gallate treated breast cancer cells suppresses tumor growth by inhibiting tumor-associated macrophage infiltration and M2 polarization. BMC Cancer, 13:421.

[40]Kanlikilicer P, Bayraktar R, Denizli M, et al., 2018. Exosomal miRNA confers chemo resistance via targeting Cav1/ p-gp/M2-type macrophage axis in ovarian cancer. EBioMedicine, 38:100-112.

[41]Kumar M, Sahu SK, Kumar R, et al., 2015. MicroRNA let-7 modulates the immune response to Mycobacterium tuberculosis infection via control of A20, an inhibitor of the NF-κB pathway. Cell Host Microbe, 17(3):345-356.

[42]Lan JQ, Sun L, Xu F, et al., 2019. M2 macrophage-derived exosomes promote cell migration and invasion in colon cancer. Cancer Res, 79(1):146-158.

[43]Li D, Duan MY, Feng Y, et al., 2016. MiR-146a modulates macrophage polarization in systemic juvenile idiopathic arthritis by targeting INHBA. Mol Immunol, 77:205-212.

[44]Li L, Sun PF, Zhang CS, et al., 2018. MiR-98 suppresses the effects of tumor-associated macrophages on promoting migration and invasion of hepatocellular carcinoma cells by regulating IL-10. Biochimie, 150:23-30.

[45]Li N, Qin JF, Han X, et al., 2018. miR-21a negatively modulates tumor suppressor genes PTEN and miR-200c and further promotes the transformation of M2 macrophages. Immunol Cell Biol, 96(1):68-80.

[46]Lin L, Lin HB, Wang L, et al., 2015. miR-130a regulates macrophage polarization and is associated with non-small cell lung cancer. Oncol Rep, 34(6):3088-3096.

[47]Lin XB, Wang SY, Sun M, et al., 2019. miR-195-5p/ NOTCH2-mediated EMT modulates IL-4 secretion in colorectal cancer to affect M2-like TAM polarization. J Hematol Oncol, 12(1):20.

[48]Liu JT, Fan LL, Yu HQ, et al., 2019. Endoplasmic reticulum stress causes liver cancer cells to release exosomal miR-23a-3p and up-regulate programmed death ligand 1 expression in macrophages. Hepatology, 70(1):241-258.

[49]Lu S, Gao Y, Huang XL, et al., 2014. Cantharidin exerts anti-hepatocellular carcinoma by miR-214 modulating macrophage polarization. Int J Biol Sci, 10(4):415-425.

[50]Martinez FO, Gordon S, 2014. The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime Rep, 6:13.

[51]Mathsyaraja H, Thies K, Taffany DA, et al., 2015. CSF1-ETS2-induced microRNA in myeloid cells promote metastatic tumor growth. Oncogene, 34(28):3651-3661.

[52]Movahedi K, Laoui D, Gysemans C, et al., 2010. Different tumor microenvironments contain functionally distinct subsets of macrophages derived from Ly6C(high) monocytes. Cancer Res, 70(14):5728-5739.

[53]Murray PJ, 2017. Macrophage polarization. Annu Rev Physiol, 79:541-566.

[54]Nahid MA, Pauley KM, Satoh M, et al., 2009. miR-146a is critical for endotoxin-induced tolerance: implication in innate immunity. J Biol Chem, 284(50):34590-34599.

[55]Nazari-Jahantigh M, Wei YY, Noels H, et al., 2012. MicroRNA-155 promotes atherosclerosis by repressing Bcl6 in macrophages. J Clin Invest, 122(11):4190-4202.

[56]Nilsson S, Moller C, Jirström K, et al., 2012. Downregulation of miR-92a is associated with aggressive breast cancer features and increased tumour macrophage infiltration. PLoS ONE, 7(4):e36051.

[57]Noy R, Pollard JW, 2014. Tumor-associated macrophages: from mechanisms to therapy. Immunity, 41(1):49-61.

[58]O'Connell RM, Chaudhuri AA, Rao DS, et al., 2009. Inositol phosphatase SHIP1 is a primary target of miR-155. Proc Natl Acad Sci USA, 106(17):7113-7118.

[59]Ouimet M, Ediriweera HN, Gundra UM, et al., 2015. MicroRNA-33-dependent regulation of macrophage metabolism directs immune cell polarization in atherosclerosis. J Clin Invest, 125(12):4334-4348.

[60]Parayath NN, Parikh A, Amiji MM, 2018. Repolarization of tumor-associated macrophages in a genetically engineered nonsmall cell lung cancer model by intraperitoneal administration of hyaluronic acid-based nanoparticles encapsulating microRNA-125b. Nano Lett, 18(6):3571-3579.

[61]Park JE, Dutta B, Tse SW, et al., 2019. Hypoxia-induced tumor exosomes promote M2-like macrophage polarization of infiltrating myeloid cells and microRNA-mediated metabolic shift. Oncogene, 38(26):5158-5173.

[62]Price NL, Rotllan N, Zhang XB, et al., 2019. Specific disruption of abca1 targeting largely mimics the effects of miR-33 knockout on macrophage cholesterol efflux and atherosclerotic plaque development. Circ Res, 124(6):874-880.

[63]Ran D, Shia WJ, Lo MC, et al., 2013. RUNX1a enhances hematopoietic lineage commitment from human embryonic stem cells and inducible pluripotent stem cells. Blood, 121(15):2882-2890.

[64]Robbins PD, Morelli AE, 2014. Regulation of immune responses by extracellular vesicles. Nat Rev Immunol, 14(3):195-208.

[65]Rosa A, Ballarino M, Sorrentino A, et al., 2007. The interplay between the master transcription factor PU.1 and miR-424 regulates human monocyte/macrophage differentiation. Proc Natl Acad Sci USA, 104(50):19849-19854.

[66]Roush S, Slack FJ, 2008. The let-7 family of microRNAs. Trends Cell Biol, 18(10):505-516.

[67]Schmid MC, Khan SQ, Kaneda MM, et al., 2018. Integrin CD11b activation drives anti-tumor innate immunity. Nat Commun, 9(1):5379.

[68]Schwarzenbach H, Nishida N, Calin GA, et al., 2014. Clinical relevance of circulating cell-free microRNAs in cancer. Nat Rev Clin Oncol, 11(3):145-156.

[69]Selimoglu-Buet D, Rivière J, Ghamlouch H, et al., 2018. A miR-150/TET3 pathway regulates the generation of mouse and human non-classical monocyte subset. Nat Commun, 9(1):5455.

[70]Sheedy FJ, Palsson-McDermott E, Hennessy EJ, et al., 2010. Negative regulation of TLR4 via targeting of the proinflammatory tumor suppressor PDCD4 by the microRNA miR-21. Nat Immunol, 11(2):141-147.

[71]Shidal C, Singh NP, Nagarkatti P, et al., 2019. MicroRNA-92 expression in CD133⁺ melanoma stem cells regulates immunosuppression in the tumor microenvironment via integrin-dependent activation of TGFβ. Cancer Res, 79(14):3622-3635.

[72]Sonda N, Simonato F, Peranzoni E, et al., 2013. miR-142-3p prevents macrophage differentiation during cancer-induced myelopoiesis. Immunity, 38(6):1236-1249.

[73]Squadrito ML, Pucci F, Magri L, et al., 2012. miR-511-3p modulates genetic programs of tumor-associated macrophages. Cell Rep, 1(2):141-154.

[74]Su SC, Zhao QY, He CH, et al., 2015. miR-142-5p and miR-130a-3p are regulated by IL-4 and IL-13 and control profibrogenic macrophage program. Nat Commun, 6:8523.

[75]Suarez-Carmona M, Lesage J, Cataldo D, et al., 2017. EMT and inflammation: inseparable actors of cancer progression. Mol Oncol, 11(7):805-823.

[76]Takano Y, Masuda T, Iinuma H, et al., 2017. Circulating exosomal microRNA-203 is associated with metastasis possibly via inducing tumor-associated macrophages in colorectal cancer. Oncotarget, 8(45):78598-78613.

[77]Talekar M, Trivedi M, Shah P, et al., 2016. Combination wt-p53 and microRNA-125b transfection in a genetically engineered lung cancer model using dual CD44/EGFR-targeting nanoparticles. Mol Ther, 24(4):759-769.

[78]Théry C, Ostrowski M, Segura E, 2009. Membrane vesicles as conveyors of immune responses. Nat Rev Immunol, 9(8):581-593.

[79]Tian YJ, Matsui S, Touma M, et al., 2018. MicroRNA-342 inhibits tumor growth via targeting chemokine CXCL12 involved in macrophages recruitment/activation. Genes Cells, 23(12):1009-1022.

[80]Tili E, Michaille JJ, Cimino A, et al., 2007. Modulation of miR-155 and miR-125b levels following lipopolysaccharide/ TNF-α stimulation and their possible roles in regulating the response to endotoxin shock. J Immunol, 179(8):5082-5089.

[81]Wang P, Hou J, Lin L, et al., 2010. Inducible microRNA-155 feedback promotes type I IFN signaling in antiviral innate immunity by targeting suppressor of cytokine signaling 1. J Immunol, 185(10):6226-6233.

[82]Wang P, Xu LJ, Qin JJ, et al., 2018. MicroRNA-155 inversely correlates with esophageal cancer progression through regulating tumor-associated macrophage FGF2 expression. Biochem Biophys Res Commun, 503(2):452-458.

[83]Wang W, Liu Y, Guo J, et al., 2018. miR-100 maintains phenotype of tumor-associated macrophages by targeting mTOR to promote tumor metastasis via Stat5a/IL-1ra pathway in mouse breast cancer. Oncogenesis, 7(12):97.

[84]Wang XF, Luo GT, Zhang KD, et al., 2018. Hypoxic tumor-derived exosomal miR-301a mediates M2 macrophage polarization via PTEN/PI3Kγ to promote pancreatic cancer metastasis. Cancer Res, 78(16):4586-4598.

[85]Wang YF, Wang BY, Xiao S, et al., 2019. miR-125a/b inhibits tumor-associated macrophages mediated in cancer stem cells of hepatocellular carcinoma by targeting CD90. J Cell Biochem, 120(3):3046-3055.

[86]Wang Z, Brandt S, Medeiros A, et al., 2015. MicroRNA 21 is a homeostatic regulator of macrophage polarization and prevents prostaglandin E₂-mediated M2 generation. PLoS ONE, 10(2):e0115855.

[87]Wei YY, Schober A, 2016. MicroRNA regulation of macrophages in human pathologies. Cell Mol Life Sci, 73(18):3473-3495.

[88]West MA, Heagy W, 2002. Endotoxin tolerance: a review. Crit Care Med, 30(1):S64-S73.

[89]Wilson WR, Hay MP, 2011. Targeting hypoxia in cancer therapy. Nat Rev Cancer, 11(6):393-410.

[90]Xi JJ, Huang Q, Wang L, et al., 2018. miR-21 depletion in macrophages promotes tumoricidal polarization and enhances PD-1 immunotherapy. Oncogene, 37(23):3151-3165.

[91]Yang J, Zhang Z, Chen C, et al., 2014. MicroRNA-19a-3p inhibits breast cancer progression and metastasis by inducing macrophage polarization through downregulated expression of Fra-1 proto-oncogene. Oncogene, 33(23):3014-3023.

[92]Yang M, Chen JQ, Su F, et al., 2011. Microvesicles secreted by macrophages shuttle invasion-potentiating microRNAs into breast cancer cells. Mol Cancer, 10:117.

[93]Yao ZY, Chen WB, Shao SS, et al., 2018. Role of exosome-associated microRNA in diagnostic and therapeutic applications to metabolic disorders. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 19(3):183-198.

[94]Ye JS, Guo RW, Shi YK, et al., 2016. miR-155 regulated inflammation response by the SOCS1-STAT3-PDCD4 axis in atherogenesis. Mediators Inflamm, 2016:8060182.

[95]Yin Y, Yao SR, Hu YL, et al., 2017. The immune-microenvironment confers chemoresistance of colorectal cancer through macrophage-derived IL6. Clin Cancer Res, 23(23):7375-7387.

[96]Ying X, Wu QF, Wu XL, et al., 2016. Epithelial ovarian cancer-secreted exosomal miR-222-3p induces polarization of tumor-associated macrophages. Oncotarget, 7(28):43076-43087.

[97]Yona S, Kim KW, Wolf Y, et al., 2013. Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis. Immunity, 38(1):79-91.

[98]Zhang J, Shan WF, Jin TT, et al., 2014. Propofol exerts anti-hepatocellular carcinoma by microvesicle-mediated transfer of miR-142-3p from macrophage to cancer cells. J Transl Med, 12:279.

[99]Zhang W, Liu H, Liu W, et al., 2015. Polycomb-mediated loss of microRNA let-7c determines inflammatory macrophage polarization via PAK1-dependent NF-κB pathway. Cell Death Differ, 22(2):287-297.

[100]Zhao HM, Wang XS, Yi P, et al., 2017. KSRP specifies monocytic and granulocytic differentiation through regulating miR-129 biogenesis and RUNX1 expression. Nat Commun, 8(1):1428.

[101]Zhao JL, Huang F, He F, et al., 2016. Forced activation of Notch in macrophages represses tumor growth by upregulating miR-125a and disabling tumor-associated macrophages. Cancer Res, 76(6):1403-1415.

[102]Zhao Y, Zou WL, Du JF, et al., 2018. The origins and homeostasis of monocytes and tissue-resident macrophages in physiological situation. J Cell Physiol, 233(10):6425-6439.

[103]Zheng PM, Chen L, Yuan XL, et al., 2017. Exosomal transfer of tumor-associated macrophage-derived miR-21 confers cisplatin resistance in gastric cancer cells. J Exp Clin Cancer Res, 36(1):53.

[104]Zhou HB, Huang XF, Cui HJ, et al., 2010. miR-155 and its star-form partner miR-155* cooperatively regulate type I interferon production by human plasmacytoid dendritic cells. Blood, 116(26):5885-5894.

[105]Zhou JR, Li XD, Wu XL, et al., 2018. Exosomes released from tumor-associated macrophages transfer miRNAs that induce a Treg/Th17 cell imbalance in epithelial ovarian cancer. Cancer Immunol Res, 6(12):1578-1592.

[106]Zhou SL, Hu ZQ, Zhou ZJ, et al., 2016. miR-28-5p-IL-34-macrophage feedback loop modulates hepatocellular carcinoma metastasis. Hepatology, 63(5):1560-1575.

[107]Zhu XL, Shen HL, Yin XM, et al., 2019. Macrophages derived exosomes deliver miR-223 to epithelial ovarian cancer cells to elicit a chemoresistant phenotype. J Exp Clin Cancer Res, 38(1):81.