1932

Abstract

Accumulation of pathologically activated immature myeloid cells with potent immune-suppressive activity is one of the major immunological hallmarks of cancer. In recent years, it became clear that in addition to their immune-suppressive activity, myeloid-derived suppressor cells (MDSCs) influence tumor progression in a variety of ways. They are directly implicated in the promotion of tumor metastases by participating in the formation of premetastatic niches, promoting angiogenesis and tumor cell invasion. In this review, we discuss recent data describing various roles of MDSCs in the formation of tumor metastases.

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2015-01-14
2024-10-04
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Literature Cited

  1. Gabrilovich DI, Ostrand-Rosenberg S, Bronte V. 1.  2012. Coordinated regulation of myeloid cells by tumours. Nat. Rev. Immunol. 12:253–68 [Google Scholar]
  2. Talmadge JE, Gabrilovich DI. 2.  2013. History of myeloid-derived suppressor cells. Nat. Rev. Cancer 13:739–52 [Google Scholar]
  3. Youn JI, Gabrilovich DI. 3.  2010. The biology of myeloid-derived suppressor cells: the blessing and the curse of morphological and functional heterogeneity. Eur. J. Immunol. 40:2969–75 [Google Scholar]
  4. Gabrilovich DI, Nagaraj S. 4.  2009. Myeloid-derived suppressor cells as regulators of the immune system. Nat. Rev. Immunol. 9:162–74 [Google Scholar]
  5. Youn JI, Nagaraj S, Collazo M, Gabrilovich DI. 5.  2008. Subsets of myeloid-derived suppressor cells in tumor-bearing mice. J. Immunol. 181:5791–802 [Google Scholar]
  6. Movahedi K, Guilliams M, Van den Bossche J. 6.  et al. 2008. Identification of discrete tumor-induced myeloid-derived suppressor cell subpopulations with distinct T cell–suppressive activity. Blood 111:4233–44 [Google Scholar]
  7. Segal AW.7.  2005. How neutrophils kill microbes. Annu. Rev. Immunol. 23:197–223 [Google Scholar]
  8. Youn JI, Collazo M, Shalova IN. 8.  et al. 2012. Characterization of the nature of granulocytic myeloid-derived suppressor cells in tumor-bearing mice. J. Leukoc. Biol. 91:167–81 [Google Scholar]
  9. Youn JI, Kumar V, Collazo M. 9.  et al. 2013. Epigenetic silencing of retinoblastoma gene regulates pathologic differentiation of myeloid cells in cancer. Nat. Immunol. 14:211–20 [Google Scholar]
  10. Corzo CA, Condamine T, Lu L. 10.  et al. 2010. HIF-1alpha regulates function and differentiation of myeloid-derived suppressor cells in the tumor microenvironment. J. Exp. Med. 207:2439–53 [Google Scholar]
  11. Greten TF, Manns MP, Korangy F. 11.  2011. Myeloid derived suppressor cells in human diseases. Int. Immunopharmacol. 11:802–7 [Google Scholar]
  12. Brandau S, Trellakis S, Bruderek K. 12.  et al. 2011. Myeloid-derived suppressor cells in the peripheral blood of cancer patients contain a subset of immature neutrophils with impaired migratory properties. J. Leukoc. Biol. 89:311–17 [Google Scholar]
  13. Rodriguez PC, Ernstoff MS, Hernandez C. 13.  et al. 2009. Arginase I-producing myeloid-derived suppressor cells in renal cell carcinoma are a subpopulation of activated granulocytes. Cancer Res. 69:1553–60 [Google Scholar]
  14. Filipazzi P, Valenti R, Huber V. 14.  et al. 2007. Identification of a new subset of myeloid suppressor cells in peripheral blood of melanoma patients with modulation by a granulocyte-macrophage colony-stimulation factor-based antitumor vaccine. J. Clin. Oncol. 25:2546–53 [Google Scholar]
  15. Poschke I, Mougiakakos D, Hansson J. 15.  et al. 2010. Immature immunosuppressive CD14+HLA–DR–/low cells in melanoma patients are Stat3hi and overexpress CD80, CD83, and DC-sign. Cancer Res. 70:4335–45 [Google Scholar]
  16. Poschke I, Kiessling R. 16.  2012. On the armament and appearances of human myeloid-derived suppressor cells. Clin. Immunol. 144:250–68 [Google Scholar]
  17. Diaz-Montero CM, Salem ML, Nishimura MI. 17.  et al. 2009. Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin-cyclophosphamide chemotherapy. Cancer Immunol. Immunother. 58:49–59 [Google Scholar]
  18. Wang L, Chang EW, Wong SC. 18.  et al. 2013. Increased myeloid-derived suppressor cells in gastric cancer correlate with cancer stage and plasma S100A8/A9 proinflammatory proteins. J. Immunol. 190:794–804 [Google Scholar]
  19. Zhang B, Wang Z, Wu L. 19.  et al. 2013. Circulating and tumor-infiltrating myeloid-derived suppressor cells in patients with colorectal carcinoma. PLOS ONE 8:e57114 [Google Scholar]
  20. Sun HL, Zhou X, Xue YF. 20.  et al. 2012. Increased frequency and clinical significance of myeloid-derived suppressor cells in human colorectal carcinoma. World J. Gastroenterol. 18:3303–9 [Google Scholar]
  21. Cui TX, Kryczek I, Zhao L. 21.  et al. 2013. Myeloid-derived suppressor cells enhance stemness of cancer cells by inducing microRNA101 and suppressing the corepressor CtBP2. Immunity 39:611–21Suggests that MDSCs can regulate stemness of tumor cells. [Google Scholar]
  22. Khaled Y, Ammori B, Elkord E. 22.  2014. Increased levels of granulocytic myeloid-derived suppressor cells in peripheral blood and tumour tissue of pancreatic cancer patients. J. Immunol. Res. 2014879897 [Google Scholar]
  23. Walter S, Weinschenk T, Stenzl A. 23.  et al. 2012. Multipeptide immune response to cancer vaccine IMA901 after single-dose cyclophosphamide associates with longer patient survival. Nat. Med. 18:1254–6123, 24. Describe the value of MDSCs as prognostic markers in patients treated with cancer vaccines. [Google Scholar]
  24. Antonia SJ, Mirza N, Fricke I. 24.  et al. 2006. Combination of p53 cancer vaccine with chemotherapy in patients with extensive stage small cell lung cancer. Clin. Cancer Res. 12:878–8723, 24. Describe the value of MDSCs as prognostic markers in patients treated with cancer vaccines. [Google Scholar]
  25. Iclozan C, Antonia S, Chiappori A. 25.  et al. 2013. Therapeutic regulation of myeloid-derived suppressor cells and immune response to cancer vaccine in patients with extensive stage small cell lung cancer. Cancer Immunol. Immunother. 62:909–18First report describing the effect of MDSC targeting in cancer patients on immune response to vaccines. [Google Scholar]
  26. Arihara F, Mizukoshi E, Kitahara M. 26.  et al. 2013. Increase in CD14+HLA-DR–/low myeloid-derived suppressor cells in hepatocellular carcinoma patients and its impact on prognosis. Cancer Immunol. Immunother. 62:1421–30 [Google Scholar]
  27. Feng PH, Lee KY, Chang YL. 27.  et al. 2012. CD14+S100A9+ monocytic myeloid-derived suppressor cells and their clinical relevance in non-small cell lung cancer. Am. J. Respir. Crit. Care Med. 186:1025–36 [Google Scholar]
  28. Huang A, Zhang B, Wang B. 28.  et al. 2013. 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. Cancer Immunol. Immunother. 62:1439–51 [Google Scholar]
  29. Meyer C, Cagnon L, Costa-Nunes CM. 29.  et al. 2014. Frequencies of circulating MDSC correlate with clinical outcome of melanoma patients treated with ipilimumab. Cancer Immunol. Immunother. 63:247–57 [Google Scholar]
  30. Condamine T, Gabrilovich DI. 30.  2011. Molecular mechanisms regulating myeloid-derived suppressor cell differentiation and function. Trends Immunol. 32:19–25 [Google Scholar]
  31. Nefedova Y, Huang M, Kusmartsev S. 31.  et al. 2004. Hyperactivation of STAT3 is involved in abnormal differentiation of dendritic cells in cancer. J. Immunol. 172:464–74 [Google Scholar]
  32. Cheng P, Corzo CA, Luetteke N. 32.  et al. 2008. Inhibition of dendritic cell differentiation and accumulation of myeloid-derived suppressor cells in cancer is regulated by S100A9 protein. J. Exp. Med. 205:2235–49 [Google Scholar]
  33. Marigo I, Bosio E, Solito S. 33.  et al. 2010. Tumor-induced tolerance and immune suppression depend on the C/EBPbeta transcription factor. Immunity 32:790–802 [Google Scholar]
  34. Waight JD, Netherby C, Hensen ML. 34.  et al. 2013. Myeloid-derived suppressor cell development is regulated by a STAT/IRF-8 axis. J. Clin. Invest. 123:4464–78 [Google Scholar]
  35. Liu Y, Xiang X, Zhuang X. 35.  et al. 2010. Contribution of MyD88 to the tumor exosome-mediated induction of myeloid derived suppressor cells. Am. J. Pathol. 176:2490–99 [Google Scholar]
  36. Martino A, Badell E, Abadie V. 36.  et al. 2010. Mycobacterium bovis bacillus Calmette-Guerin vaccination mobilizes innate myeloid-derived suppressor cells restraining in vivo T cell priming via IL-1R-dependent nitric oxide production. J. Immunol. 184:2038–47 [Google Scholar]
  37. Sinha P, Clements VK, Fulton AM, Ostrand-Rosenberg S. 37.  2007. Prostaglandin E2 promotes tumor progression by inducing myeloid-derived suppressor cells. Cancer Res. 67:4507–13 [Google Scholar]
  38. Zhang Y, Liu Q, Zhang M. 38.  et al. 2009. Fas signal promotes lung cancer growth by recruiting myeloid-derived suppressor cells via cancer cell-derived PGE2. J. Immunol. 182:3801–8 [Google Scholar]
  39. Zhao X, Rong L, Zhao X. 39.  et al. 2012. TNF signaling drives myeloid-derived suppressor cell accumulation. J. Clin. Invest. 122:4094–104 [Google Scholar]
  40. Nagaraj S, Gupta K, Pisarev V. 40.  et al. 2007. Altered recognition of antigen is a mechanism of CD8+ T cell tolerance in cancer. Nat. Med. 13:828–35 [Google Scholar]
  41. Lu T, Ramakrishnan R, Altiok S. 41.  et al. 2011. Tumor-infiltrating myeloid cells induce tumor cell resistance to cytotoxic T cells in mice. J. Clin. Invest. 121:4015–29 [Google Scholar]
  42. Rodriguez PC, Zea AH, Culotta KS. 42.  et al. 2002. Regulation of T cell receptor CD3zeta chain expression by L-arginine. J. Biol. Chem. 277:21123–29 [Google Scholar]
  43. Zea AH, Rodriguez PC, Atkins MB. 43.  et al. 2005. Arginase-producing myeloid suppressor cells in renal cell carcinoma patients: a mechanism of tumor evasion. Cancer Res. 65:3044–48 [Google Scholar]
  44. Srivastava MK, Sinha P, Clements VK. 44.  et al. 2010. Myeloid-derived suppressor cells inhibit T-cell activation by depleting cystine and cysteine. Cancer Res. 70:68–77 [Google Scholar]
  45. Huang B, Pan PY, Li Q. 45.  et al. 2006. Gr-1+CD115+ immature myeloid suppressor cells mediate the development of tumor-induced T regulatory cells and T-cell anergy in tumor-bearing host. Cancer Res. 66:1123–31 [Google Scholar]
  46. Yang R, Cai Z, Zhang Y. 46.  et al. 2006. CD80 in immune suppression by mouse ovarian carcinoma-associated Gr-1+CD11b+ myeloid cells. Cancer Res. 66:6807–15 [Google Scholar]
  47. Pan PY, Ma G, Weber KJ. 47.  et al. 2010. Immune stimulatory receptor CD40 is required for T-cell suppression and T regulatory cell activation mediated by myeloid-derived suppressor cells in cancer. Cancer Res. 70:99–108 [Google Scholar]
  48. Serafini P, Mgebroff S, Noonan K, Borrello I. 48.  2008. Myeloid-derived suppressor cells promote cross-tolerance in B-cell lymphoma by expanding regulatory T cells. Cancer Res. 68:5439–49 [Google Scholar]
  49. Schlecker E, Stojanovic A, Eisen C. 49.  et al. 2012. Tumor-infiltrating monocytic myeloid-derived suppressor cells mediate CCR5-dependent recruitment of regulatory T cells favoring tumor growth. J. Immunol. 189:5602–11 [Google Scholar]
  50. Hoechst B, Gamrekelashvili J, Manns MP. 50.  et al. 2011. Plasticity of human Th17 cells and iTregs is orchestrated by different subsets of myeloid cells. Blood 117:6532–41 [Google Scholar]
  51. Centuori SM, Trad M, LaCasse CJ. 51.  et al. 2012. Myeloid-derived suppressor cells from tumor-bearing mice impair TGF-beta-induced differentiation of CD4+CD25+FoxP3+ Tregs from CD4+CD25–FoxP3– T cells. J. Leukoc. Biol. 92:987–97 [Google Scholar]
  52. Novitskiy SV, Pickup MW, Gorska AE. 52.  et al. 2011. TGF-beta receptor II loss promotes mammary carcinoma progression by Th17 dependent mechanisms. Cancer Discov. 1:430–41 [Google Scholar]
  53. Hu X, Li B, Li X. 53.  et al. 2014. Transmembrane TNF-alpha promotes suppressive activities of myeloid-derived suppressor cells via TNFR2. J. Immunol. 192:1320–31 [Google Scholar]
  54. Yu J, Du W, Yan F. 54.  et al. 2013. Myeloid-derived suppressor cells suppress antitumor immune responses through IDO expression and correlate with lymph node metastasis in patients with breast cancer. J. Immunol. 190:3783–97 [Google Scholar]
  55. Achberger S, Aldrich W, Tubbs R. 55.  et al. 2013. Circulating immune cell and microRNA in patients with uveal melanoma developing metastatic disease. Mol. Immunol. 58:182–86 [Google Scholar]
  56. Weide B, Martens A, Zelba H. 56.  et al. 2014. Myeloid-derived suppressor cells predict survival of patients with advanced melanoma: comparison with regulatory T cells and NY-ESO-1- or melan-A-specific T cells. Clin. Cancer Res. 20:1601–9 [Google Scholar]
  57. Sander LE, Sackett SD, Dierssen U. 57.  et al. 2010. Hepatic acute-phase proteins control innate immune responses during infection by promoting myeloid-derived suppressor cell function. J. Exp. Med. 207:1453–64 [Google Scholar]
  58. Acharyya S, Oskarsson T, Vanharanta S. 58.  et al. 2012. A CXCL1 paracrine network links cancer chemoresistance and metastasis. Cell 150:165–78 [Google Scholar]
  59. Connolly MK, Mallen–St Clair J, Bedrosian AS. 59.  et al. 2010. Distinct populations of metastases-enabling myeloid cells expand in the liver of mice harboring invasive and preinvasive intra-abdominal tumor. J. Leukoc. Biol. 87:713–25 [Google Scholar]
  60. Toh B, Wang X, Keeble J. 60.  et al. 2011. Mesenchymal transition and dissemination of cancer cells is driven by myeloid-derived suppressor cells infiltrating the primary tumor. PLOS Biol. 9:e1001162 [Google Scholar]
  61. Katoh H, Wang D, Daikoku T. 61.  et al. 2013. CXCR2-expressing myeloid-derived suppressor cells are essential to promote colitis-associated tumorigenesis. Cancer Cell 24:631–44This study using genetically modified MDSCs (lacking CXCR2) demonstrated a direct role of these cells in colitis-induced carcinogenesis. [Google Scholar]
  62. Obermajer N, Muthuswamy R, Odunsi K. 62.  et al. 2011. PGE2-induced CXCL12 production and CXCR4 expression controls the accumulation of human MDSCs in ovarian cancer environment. Cancer Res. 71:7463–70 [Google Scholar]
  63. Huang B, Lei Z, Zhao J. 63.  et al. 2007. CCL2/CCR2 pathway mediates recruitment of myeloid suppressor cells to cancers. Cancer Lett. 252:86–92 [Google Scholar]
  64. Lesokhin AM, Hohl TM, Kitano S. 64.  et al. 2012. Monocytic CCR2+ myeloid-derived suppressor cells promote immune escape by limiting activated CD8 T-cell infiltration into the tumor microenvironment. Cancer Res. 72:876–86 [Google Scholar]
  65. Sawanobori Y, Ueha S, Kurachi M. 65.  et al. 2008. Chemokine-mediated rapid turnover of myeloid-derived suppressor cells in tumor-bearing mice. Blood 111:5457–66 [Google Scholar]
  66. Molon B, Ugel S, Del Pozzo F. 66.  et al. 2011. Chemokine nitration prevents intratumoral infiltration of antigen-specific T cells. J. Exp. Med. 208:1949–62 [Google Scholar]
  67. Simpson KD, Templeton DJ, Cross JV. 67.  2012. Macrophage migration inhibitory factor promotes tumor growth and metastasis by inducing myeloid-derived suppressor cells in the tumor microenvironment. J. Immunol. 189:5533–40 [Google Scholar]
  68. Simpson KD, Cross JV. 68.  2013. MIF: metastasis/MDSC-inducing factor?. Oncoimmunology 2:e23337 [Google Scholar]
  69. Sinha P, Okoro C, Foell D. 69.  et al. 2008. Proinflammatory s100 proteins regulate the accumulation of myeloid-derived suppressor cells. J. Immunol. 181:4666–75 [Google Scholar]
  70. Hiratsuka S, Watanabe A, Aburatani H, Maru Y. 70.  2006. Tumour-mediated upregulation of chemoattractants and recruitment of myeloid cells predetermines lung metastasis. Nat. Cell Biol. 8:1369–75 [Google Scholar]
  71. Ichikawa M, Williams R, Wang L. 71.  et al. 2011. S100A8/A9 activate key genes and pathways in colon tumor progression. Mol. Cancer Res. 9:133–48 [Google Scholar]
  72. Hiratsuka S, Watanabe A, Sakurai Y. 72.  et al. 2008. The S100A8-serum amyloid A3-TLR4 paracrine cascade establishes a pre-metastatic phase. Nat. Cell Biol. 10:1349–55 [Google Scholar]
  73. Du R, Lu KV, Petritsch C. 73.  et al. 2008. HIF1alpha induces the recruitment of bone marrow–derived vascular modulatory cells to regulate tumor angiogenesis and invasion. Cancer Cell 13:206–20 [Google Scholar]
  74. Ye XZ, Yu SC, Bian XW. 74.  2010. Contribution of myeloid-derived suppressor cells to tumor-induced immune suppression, angiogenesis, invasion and metastasis. J. Genet. Genomics 37:423–30 [Google Scholar]
  75. Pan PY, Wang GX, Yin B. 75.  et al. 2008. Reversion of immune tolerance in advanced malignancy: modulation of myeloid-derived suppressor cell development by blockade of stem-cell factor function. Blood 111:219–28 [Google Scholar]
  76. Qu X, Zhuang G, Yu L. 76.  et al. 2012. Induction of Bv8 expression by granulocyte colony-stimulating factor in CD11b+Gr1+ cells: key role of Stat3 signaling. J. Biol. Chem. 287:19574–84 [Google Scholar]
  77. Kujawski M, Kortylewski M, Lee H. 77.  et al. 2008. Stat3 mediates myeloid cell-dependent tumor angiogenesis in mice. J. Clin. Invest. 118:3367–77 [Google Scholar]
  78. Kowanetz M, Wu X, Lee J. 78.  et al. 2010. Granulocyte-colony stimulating factor promotes lung metastasis through mobilization of Ly6G+Ly6C+ granulocytes. Proc. Natl. Acad. Sci. USA 107:21248–55 [Google Scholar]
  79. Shojaei F, Wu X, Zhong C. 79.  et al. 2007. Bv8 regulates myeloid-cell-dependent tumour angiogenesis. Nature 450:825–31 [Google Scholar]
  80. Yang L, DeBusk LM, Fukuda K. 80.  et al. 2004. Expansion of myeloid immune suppressor Gr+CD11b+ cells in tumor-bearing host directly promotes tumor angiogenesis. Cancer Cell 6:409–21 [Google Scholar]
  81. Priceman SJ, Sung JL, Shaposhnik Z. 81.  et al. 2010. Targeting distinct tumor-infiltrating myeloid cells by inhibiting CSF-1 receptor: combating tumor evasion of antiangiogenic therapy. Blood 115:1461–71 [Google Scholar]
  82. Shojaei F, Wu X, Malik AK. 82.  et al. 2007. Tumor refractoriness to anti-VEGF treatment is mediated by CD11b+Gr1+ myeloid cells. Nat. Biotechnol. 25:911–20 [Google Scholar]
  83. Finke J, Ko J, Rini B. 83.  et al. 2011. MDSC as a mechanism of tumor escape from sunitinib mediated anti-angiogenic therapy. Int. Immunopharmacol. 11:856–61 [Google Scholar]
  84. Yang L, Huang J, Ren X. 84.  et al. 2008. Abrogation of TGF beta signaling in mammary carcinomas recruits Gr-1+CD11b+ myeloid cells that promote metastasis. Cancer Cell 13:23–35 [Google Scholar]
  85. Boutte AM, Friedman DB, Bogyo M. 85.  et al. 2011. Identification of a myeloid-derived suppressor cell cystatin-like protein that inhibits metastasis. FASEB J. 25:2626–37 [Google Scholar]
  86. Kitamura T, Kometani K, Hashida H. 86.  et al. 2007. SMAD4-deficient intestinal tumors recruit CCR1+ myeloid cells that promote invasion. Nat. Genet. 39:467–75 [Google Scholar]
  87. Pang Y, Gara SK, Achyut BR. 87.  et al. 2013. TGF-beta signaling in myeloid cells is required for tumor metastasis. Cancer Discov. 3:936–51Demonstrated a direct role of myeloid-derived TGF-β in promoting tumor metastases. [Google Scholar]
  88. Oh K, Lee OY, Shon SY. 88.  et al. 2013. A mutual activation loop between breast cancer cells and myeloid-derived suppressor cells facilitates spontaneous metastasis through IL-6 trans-signaling in a murine model. Breast Cancer Res. 15:R79 [Google Scholar]
  89. Kuonen F, Laurent J, Secondini C. 89.  et al. 2012. Inhibition of the Kit ligand/c-Kit axis attenuates metastasis in a mouse model mimicking local breast cancer relapse after radiotherapy. Clin. Cancer Res. 18:4365–74 [Google Scholar]
  90. Sceneay J, Chow MT, Chen A. 90.  et al. 2012. Primary tumor hypoxia recruits CD11b+/Ly6Cmed/Ly6G+ immune suppressor cells and compromises NK cell cytotoxicity in the premetastatic niche. Cancer Res. 72:3906–11 [Google Scholar]
  91. Gao D, Vahdat LT, Wong S. 91.  et al. 2012. Microenvironmental regulation of epithelial-mesenchymal transitions in cancer. Cancer Res. 72:4883–89 [Google Scholar]
  92. Panni RZ, Sanford DE, Belt BA. 92.  et al. 2014. Tumor-induced STAT3 activation in monocytic myeloid-derived suppressor cells enhances stemness and mesenchymal properties in human pancreatic cancer. Cancer Immunol. Immunother. 63:513–28 [Google Scholar]
  93. Yan HH, Pickup M, Pang Y. 93.  et al. 2010. Gr-1+CD11b+ myeloid cells tip the balance of immune protection to tumor promotion in the premetastatic lung. Cancer Res. 70:6139–49MDSCs implicated in MET. [Google Scholar]
  94. Gao D, Joshi N, Choi H. 94.  et al. 2012. Myeloid progenitor cells in the premetastatic lung promote metastases by inducing mesenchymal to epithelial transition. Cancer Res. 72:1384–94 [Google Scholar]
  95. Sawant A, Deshane J, Jules J. 95.  et al. 2013. Myeloid-derived suppressor cells function as novel osteoclast progenitors enhancing bone loss in breast cancer. Cancer Res. 73:672–82Interesting report indicating antimetastatic role of MDSCs. [Google Scholar]
  96. Catena R, Bhattacharya N, El Rayes T. 96.  et al. 2013. Bone marrow-derived Gr1+ cells can generate a metastasis-resistant microenvironment via induced secretion of thrombospondin-1. Cancer Discov. 3:578–89 [Google Scholar]
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