The pro-metastatic role of bone marrow-derived cells: A focus on MSCs and regulatory T cells

EMBO Reports

Volumn 13, Issue 5, 2012, Pages 412-422

  Koh, Bong Ihn ^a   Kang, Yibin ^a,b  

^a PRINCETON UNIVERSITY   (United States)

^b RUTGERS CANCER INSTITUTE OF NEW JERSEY   (United States)

Author keywords

bone marrow derived cells; cancer metastasis; mesenchymal stem cells; regulatory T cells

Indexed keywords

B LYMPHOCYTE; CELL FUNCTION; CELL HOMING; HUMAN; IMMUNE RESPONSE; IMMUNOMODULATION; IMMUNOSUPPRESSIVE TREATMENT; MESENCHYMAL STEM CELL; METASTASIS; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; REVIEW; SIGNAL TRANSDUCTION; TUMOR GROWTH; TUMOR MICROENVIRONMENT;

ANIMALS; BONE MARROW CELLS; HUMANS; MESENCHYMAL STEM CELLS; NEOPLASM METASTASIS; T-LYMPHOCYTES, REGULATORY;

EID: 84860432909     PISSN: 1469221X     EISSN: 14693178     Source Type: Journal    
DOI: 10.1038/embor.2012.41     Document Type: Review

References (204)

1. Gupta GP, Massague J (2006) Cancer metastasis: building a framework. Cell 127: 679-695 (Pubitemid 44781029)
2. Valastyan S, Weinberg RA (2011) Tumor metastasis: molecular insights and evolving paradigms. Cell 147: 275-292
3. Nguyen DX, Bos PD, Massague J (2009) Metastasis: from dissemination to organ-specific colonization. Nat Rev Cancer 9: 274-284
4. Joyce JA, Pollard JW (2009) Microenvironmental regulation of metastasis. Nat Rev Cancer 9: 239-252
5. Erez N, Coussens LM (2011) Leukocytes as paracrine regulators of metastasis and determinants of organ-specific colonization. Int J Cancer 128: 2536-2544
6. Paget S (1889) The distribution of secondary growths in cancer of the breast. Lancet 133: 571-573
7. Bos PD et al (2009) Genes that mediate breast cancer metastasis to the brain. Nature 459: 1005-1009
8. Kang Y, Siegel PM, Shu W, Drobnjak M, Kakonen SM, Cordon-Cardo C, Guise TA, Massague J (2003) A multigenic program mediating breast cancer metastasis to bone. Cancer Cell 3: 537-549 (Pubitemid 36808649)
9. Minn AJ et al (2005) Genes that mediate breast cancer metastasis to lung. Nature 436: 518-524 (Pubitemid 41112921)
10. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144: 646-674
11. Klopp AH, Gupta A, Spaeth E, Andreeff M, Marini F 3rd (2011) Dissecting a discrepancy in the literature: do mesenchymal stem cells support or suppress tumor growth? Stem Cells 29: 11-19
12. Bergfeld SA, DeClerck YA (2010) Bone marrow-derived mesenchymal stem cells and the tumor microenvironment. Cancer Metastasis Rev 29: 249-261
13. Karnoub AE et al (2007) Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature 449: 557-563 (Pubitemid 47525152)
14. Spaeth EL, Dembinski JL, Sasser AK, Watson K, Klopp A, Hall B, Andreeff M, Marini F (2009) Mesenchymal stem cell transition to tumor-associated fibroblasts contributes to fibrovascular network expansion and tumor progression. PLoS ONE 4: e4992
15. Campbell DJ, Koch MA (2011) Phenotypical and functional specialization of FOXP3+ regulatory T cells. Nat Rev Immunol 11: 119-130
16. Curiel TJ et al (2004) Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 10: 942-949 (Pubitemid 39273735)
17. Bates GJ, Fox SB, Han C, Leek RD, Garcia JF, Harris AL, Banham AH (2006) Quantification of regulatory T cells enables the identification of high-risk breast cancer patients and those at risk of late relapse. J Clin Oncol 24: 5373-5380 (Pubitemid 46623168)
18. Mi Z, Bhattacharya SD, Kim VM, Guo H, Talbot LJ, Kuo PC (2011) Osteopontin promotes CCL5-mesenchymal stromal cell-mediated breast cancer metastasis. Carcinogenesis 32: 477-487
19. Tan W, Zhang W, Strasner A, Grivennikov S, Cheng JQ, Hoffman RM, Karin M (2011) Tumour-infiltrating regulatory T cells stimulate mammary cancer metastasis through RANKL-RANK signalling. Nature 470: 548-553
20. Stagg J, Divisekera U, Duret H, Sparwasser T, Teng MW, Darcy PK, Smyth MJ (2011) CD73-deficient mice have increased antitumor immunity and are resistant to experimental metastasis. Cancer Res 71: 2892-2900
21. Manjili MH (2011) Revisiting cancer immunoediting by understanding cancer immune complexity. J Pathol 224: 5-9
22. Qin Z, Blankenstein T (2004) A cancer immunosurveillance controversy. Nat Immunol 5: 3-5
23. Willimsky G, Blankenstein T (2005) Sporadic immunogenic tumours avoid destruction by inducing T-cell tolerance. Nature 437: 141-146 (Pubitemid 41613441)
24. Kitamura T et al (2007) SMAD4-deficient intestinal tumors recruit CCR1+ myeloid cells that promote invasion. Nat Genet 39: 467-475 (Pubitemid 46514777)
25. Kaplan RN et al (2005) VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature 438: 820-827 (Pubitemid 41753060)
26. Hiratsuka S, Watanabe A, Aburatani H, Maru Y (2006) Tumour-mediated upregulation of chemoattractants and recruitment of myeloid cells predetermines lung metastasis. Nat Cell Biol 8: 1369-1375 (Pubitemid 44835111)
27. Liu J, Zhang Y, Zhao J, Yang Z, Li D, Katirai F, Huang B (2011) Mast cell: insight into remodeling a tumor microenvironment. Cancer Metastasis Rev 30: 177-184
28. Strouch MJ et al (2010) Crosstalk between mast cells and pancreatic cancer cells contributes to pancreatic tumor progression. Clin Cancer Res 16: 2257-2265
29. Gocheva V, Wang HW, Gadea BB, Shree T, Hunter KE, Garfall AL, Berman T, Joyce JA (2010) IL-4 induces cathepsin protease activity in tumor-associated macrophages to promote cancer growth and invasion. Genes Dev 24: 241-255
30. Qian BZ, Li J, Zhang H, Kitamura T, Zhang J, Campion LR, Kaiser EA, Snyder LA, Pollard JW (2011) CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis. Nature 475: 222-225
31. Gay LJ, Felding-Habermann B (2011) Contribution of platelets to tumour metastasis. Nat Rev Cancer 11: 123-134
32. Labelle M, Begum S, Hynes RO (2011) Direct signaling between platelets and cancer cells induces an epithelial-mesenchymal-like transition and promotes metastasis. Cancer Cell 20: 576-590
33. Huh SJ, Liang S, Sharma A, Dong C, Robertson GP (2010) Transiently entrapped circulating tumor cells interact with neutrophils to facilitate lung metastasis development. Cancer Res 70: 6071-6082
34. Ergun S, Hohn HP, Kilic N, Singer BB, Tilki D (2008) Endothelial and hematopoietic progenitor cells (EPCs and HPCs): hand in hand fate determining partners for cancer cells. Stem Cell Rev 4: 169-177
35. Gao D, Nolan DJ, Mellick AS, Bambino K, McDonnell K, Mittal V (2008) Endothelial progenitor cells control the angiogenic switch in mouse lung metastasis. Science 319: 195-198
36. Kerbel RS et al (2008) Endothelial progenitor cells are cellular hubs essential for neoangiogenesis of certain aggressive adenocarcinomas and metastatic transition but not adenomas. Proc Natl Acad Sci USA 105: E54-E55
37. Talmadge JE (2011) Immune cell infiltration of primary and metastatic lesions: mechanisms and clinical impact. Semin Cancer Biol 21: 131-138
38. Grivennikov SI, Greten FR, Karin M (2010) Immunity, inflammation, and cancer. Cell 140: 883-899
39. DeNardo DG, Johansson M, Coussens LM (2008) Immune cells as mediators of solid tumor metastasis. Cancer Metastasis Rev 27: 11-18
40. Qian BZ, Pollard JW (2010) Macrophage diversity enhances tumor progression and metastasis. Cell 141: 39-51
41. Adams GB, Scadden DT (2006) The hematopoietic stem cell in its place. Nat Immunol 7: 333-337
42. Calvi LM et al (2003) Osteoblastic cells regulate the haematopoietic stem cell niche. Nature 425: 841-846 (Pubitemid 37351468)
43. Kiel MJ, Yilmaz OH, Iwashita T, Terhorst C, Morrison SJ (2005) SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell 121: 1109-1121 (Pubitemid 40884400)
44. Tokoyoda K, Hauser AE, Nakayama T, Radbruch A (2010) Organization of immunological memory by bone marrow stroma. Nat Rev Immunol 10: 193-200
45. Tokoyoda K, Egawa T, Sugiyama T, Choi BI, Nagasawa T (2004) Cellular niches controlling B lymphocyte behavior within bone marrow during development. Immunity 20: 707-718 (Pubitemid 38757441)
46. Tokoyoda K, Zehentmeier S, Hegazy AN, Albrecht I, Grun JR, Lohning M, Radbruch A (2009) Professional memory CD4+ T lymphocytes preferentially reside and rest in the bone marrow. Immunity 30: 721-730
47. Pittenger MF et al (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284: 143-147 (Pubitemid 29282067)
48. Jiang Y et al (2002) Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 418: 41-49 (Pubitemid 34742565)
49. Bianco P, Robey PG, Simmons PJ (2008) Mesenchymal stem cells: revisiting history, concepts, and assays. Cell Stem Cell 2: 313-319 (Pubitemid 351467394)
50. Bellini A, Mattoli S (2007) The role of the fibrocyte, a bone marrow-derived mesenchymal progenitor, in reactive and reparative fibroses. Lab Invest 87: 858-870 (Pubitemid 47267815)
51. Lee CH, Shah B, Moioli EK, Mao JJ (2010) CTGF directs fibroblast differentiation from human mesenchymal stem/stromal cells and defines connective tissue healing in a rodent injury model. J Clin Invest 120: 3340-3349
52. Morikawa S et al (2009) Prospective identification, isolation, and systemic transplantation of multipotent mesenchymal stem cells in murine bone marrow. J Exp Med 206: 2483-2496
53. Sacchetti B et al (2007) Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment. Cell 131: 324-336 (Pubitemid 47592917)
54. Paquet-Fifield S et al (2009) A role for pericytes as microenvironmental regulators of human skin tissue regeneration. J Clin Invest 119: 2795-2806
55. Covas DT et al (2008) Multipotent mesenchymal stromal cells obtained from diverse human tissues share functional properties and gene-expression profile with CD146+ perivascular cells and fibroblasts. Exp Hematol 36: 642-654
56. Sudo K, Kanno M, Miharada K, Ogawa S, Hiroyama T, Saijo K, Nakamura Y (2007) Mesenchymal progenitors able to differentiate into osteogenic, chondrogenic, and/or adipogenic cells in vitro are present in most primary fibroblast-like cell populations. Stem Cells 25: 1610-1617 (Pubitemid 47121837)
57. Wakitani S, Saito T, Caplan AI (1995) Myogenic cells derived from rat bone marrow mesenchymal stem cells exposed to 5-azacytidine. Muscle Nerve 18: 1417-1426
58. Kopen GC, Prockop DJ, Phinney DG (1999) Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains. Proc Natl Acad Sci USA 96: 10711-10716 (Pubitemid 29442209)
59. Sato Y et al (2005) Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion. Blood 106: 756-763 (Pubitemid 40981278)
60. Pevsner-Fischer M, Levin S, Zipori D (2011) The origins of mesenchymal stromal cell heterogeneity. Stem Cell Rev 7: 560-568
61. Dominici M et al (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8: 315-317 (Pubitemid 44269669)
62. Bonyadi M, Waldman SD, Liu D, Aubin JE, Grynpas MD, Stanford WL (2003) Mesenchymal progenitor self-renewal deficiency leads to age-dependent osteoporosis in Sca-1/Ly-6A null mice. Proc Natl Acad Sci USA 100: 5840-5845 (Pubitemid 36576895)
63. Rada T, Reis RL, Gomes ME (2011) Distinct stem cells subpopulations isolated from human adipose tissue exhibit different chondrogenic and osteogenic differentiation potential. Stem Cell Rev 7: 64-76
64. Dubois SG, Floyd EZ, Zvonic S, Kilroy G, Wu X, Carling S, Halvorsen YD, Ravussin E, Gimble JM (2008) Isolation of human adipose-derived stem cells from biopsies and liposuction specimens. Methods Mol Biol 449: 69-79
65. Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, Benhaim P, Lorenz HP, Hedrick MH (2001) Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng 7: 211-228 (Pubitemid 32295155)
66. Romanov YA, Svintsitskaya VA, Smirnov VN (2003) Searching for alternative sources of postnatal human mesenchymal stem cells: candidate MSC-like cells from umbilical cord. Stem Cells 21: 105-110 (Pubitemid 36120371)
67. Wang HS, Hung SC, Peng ST, Huang CC, Wei HM, Guo YJ, Fu YS, Lai MC, Chen CC (2004) Mesenchymal stem cells in the Wharton's jelly of the human umbilical cord. Stem Cells 22: 1330-1337
68. da Silva Meirelles L, Chagastelles PC, Nardi NB (2006) Mesenchymal stem cells reside in virtually all post-natal organs and tissues. J Cell Sci 119: 2204-2213 (Pubitemid 43960310)
69. Panepucci RA, Siufi JL, Silva WA Jr, Proto-Siquiera R, Neder L, Orellana M, Rocha V, Covas DT, Zago MA (2004) Comparison of gene expression of umbilical cord vein and bone marrow-derived mesenchymal stem cells. Stem Cells 22: 1263-1278 (Pubitemid 39646504)
70. Kaltz N, Ringe J, Holzwarth C, Charbord P, Niemeyer M, Jacobs VR, Peschel C, Haupl T, Oostendorp RA (2010) Novel markers of mesenchymal stem cells defined by genome-wide gene expression analysis of stromal cells from different sources. Exp Cell Res 316: 2609-2617
71. Winter A, Breit S, Parsch D, Benz K, Steck E, Hauner H, Weber RM, Ewerbeck V, Richter W (2003) Cartilage-like gene expression in differentiated human stem cell spheroids: a comparison of bone marrow-derived and adipose tissue-derived stromal cells. Arthritis Rheum 48: 418-429 (Pubitemid 36278011)
72. Cowan CM et al (2004) Adipose-derived adult stromal cells heal critical-size mouse calvarial defects. Nat Biotechnol 22: 560-567 (Pubitemid 38585908)
73. Awad HA, Wickham MQ, Leddy HA, Gimble JM, Guilak F (2004) Chondrogenic differentiation of adipose-derived adult stem cells in agarose, alginate, and gelatin scaffolds. Biomaterials 25: 3211-3222 (Pubitemid 38234782)
74. Erickson GR, Gimble JM, Franklin DM, Rice HE, Awad H, Guilak F (2002) Chondrogenic potential of adipose tissue-derived stromal cells in vitro and in vivo. Biochem Biophys Res Commun 290: 763-769 (Pubitemid 34687506)
75. Rodriguez AM et al (2005) Transplantation of a multipotent cell population from human adipose tissue induces dystrophin expression in the immunocompetent mdx mouse. J Exp Med 201: 1397-1405
76. Miranville A, Heeschen C, Sengenes C, Curat CA, Busse R, Bouloumie A (2004) Improvement of postnatal neovascularization by human adipose tissue-derived stem cells. Circulation 110: 349-355 (Pubitemid 38955505)
77. Planat-Benard V et al (2004) Plasticity of human adipose lineage cells toward endothelial cells: physiological and therapeutic perspectives. Circulation 109: 656-663 (Pubitemid 38198874)
78. Yagi K, Kondo D, Okazaki Y, Kano K (2004) A novel preadipocyte cell line established from mouse adult mature adipocytes. Biochem Biophys Res Commun 321: 967-974 (Pubitemid 39044403)
79. Matsumoto T et al (2008) Mature adipocyte-derived dedifferentiated fat cells exhibit multilineage potential. J Cell Physiol 215: 210-222 (Pubitemid 351363206)
80. Oki Y, Watanabe S, Endo T, Kano K (2008) Mature adipocyte-derived dedifferentiated fat cells can trans-differentiate into osteoblasts in vitro and in vivo only by all-trans retinoic acid. Cell Struct Funct 33: 211-222
81. Stappenbeck TS, Miyoshi H (2009) The role of stromal stem cells in tissue regeneration and wound repair. Science 324: 1666-1669
82. Morigi M et al (2008) Human bone marrow mesenchymal stem cells accelerate recovery of acute renal injury and prolong survival in mice. Stem Cells 26: 2075-2082
83. Chen L, Tredget EE, Wu PY, Wu Y (2008) Paracrine factors of mesenchymal stem cells recruit macrophages and endothelial lineage cells and enhance wound healing. PLoS ONE 3: e1886
84. Oh JY, Kim MK, Shin MS, Lee HJ, Ko JH, Wee WR, Lee JH (2008) The anti-inflammatory and anti-angiogenic role of mesenchymal stem cells in corneal wound healing following chemical injury. Stem Cells 26: 1047-1055
85. Mishra PJ, Glod JW, Banerjee D (2009) Mesenchymal stem cells: flip side of the coin. Cancer Res 69: 1255-1258
86. Mishra PJ, Humeniuk R, Medina DJ, Alexe G, Mesirov JP, Ganesan S, Glod JW, Banerjee D (2008) Carcinoma-associated fibroblast-like differentiation of human mesenchymal stem cells. Cancer Res 68: 4331-4339
87. Quante M et al (2011) Bone marrow-derived myofibroblasts contribute to the mesenchymal stem cell niche and promote tumor growth. Cancer Cell 19: 257-272
88. Beckermann BM et al (2008) VEGF expression by mesenchymal stem cells contributes to angiogenesis in pancreatic carcinoma. Br J Cancer 99: 622-631
89. Dvorak HF (1986) Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med 315: 1650-1659 (Pubitemid 17052899)
90. Zhu W, Xu W, Jiang R, Qian H, Chen M, Hu J, Cao W, Han C, Chen Y (2006) Mesenchymal stem cells derived from bone marrow favor tumor cell growth in vivo. Exp Mol Pathol 80: 267-274
91. Djouad F, Plence P, Bony C, Tropel P, Apparailly F, Sany J, Noel D, Jorgensen C (2003) Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals. Blood 102: 3837-3844 (Pubitemid 37409409)
92. Shinagawa K, Kitadai Y, Tanaka M, Sumida T, Kodama M, Higashi Y, Tanaka S, Yasui W, Chayama K (2010) Mesenchymal stem cells enhance growth and metastasis of colon cancer. Int J Cancer 127: 2323-2333
93. Goldstein RH, Reagan MR, Anderson K, Kaplan DL, Rosenblatt M (2010) Human bone marrow-derived MSCs can home to orthotopic breast cancer tumors and promote bone metastasis. Cancer Res 70: 10044-10050
94. Oskarsson T et al (2011) Breast cancer cells produce tenascin C as a metastatic niche component to colonize the lungs. Nat Med 17: 867-874
95. Kalluri R, Zeisberg M (2006) Fibroblasts in cancer. Nat Rev Cancer 6: 392-401
96. Micke P, Ostman A (2005) Exploring the tumour environment: cancer-associated fibroblasts as targets in cancer therapy. Expert Opin Ther Targets 9: 1217-1233 (Pubitemid 41762875)
97. Boire A, Covic L, Agarwal A, Jacques S, Sherifi S, Kuliopulos A (2005) PAR1 is a matrix metalloprotease-1 receptor that promotes invasion and tumorigenesis of breast cancer cells. Cell 120: 303-313 (Pubitemid 40222426)
98. Eck SM, Cote AL, Winkelman WD, Brinckerhoff CE (2009) CXCR4 and matrix metalloproteinase-1 are elevated in breast carcinoma-associated fibroblasts and in normal mammary fibroblasts exposed to factors secreted by breast cancer cells. Mol Cancer Res 7: 1033-1044
99. Olumi AF, Dazin P, Tlsty TD (1998) A novel coculture technique demonstrates that normal human prostatic fibroblasts contribute to tumor formation of LNCaP cells by retarding cell death. Cancer Res 58: 4525-4530 (Pubitemid 28480607)
100. Olumi AF, Grossfeld GD, Hayward SW, Carroll PR, Tlsty TD, Cunha GR (1999) Carcinoma-associated fibroblasts direct tumor progression of initiated human prostatic epithelium. Cancer Res 59: 5002-5011 (Pubitemid 29472907)
101. Duda DG, Duyverman AM, Kohno M, Snuderl M, Steller EJ, Fukumura D, Jain RK (2010) Malignant cells facilitate lung metastasis by bringing their own soil. Proc Natl Acad Sci USA 107: 21677-21682
102. Sung SY et al (2008) Coevolution of prostate cancer and bone stroma in three-dimensional coculture: implications for cancer growth and metastasis. Cancer Res 68: 9996-10003
103. Malanchi I, Santamaria-Martinez A, Susanto E, Peng H, Lehr HA, Delaloye JF, Huelsken J (2012) Interactions between cancer stem cells and their niche govern metastatic colonization. Nature 481: 85-89
104. Psaila B, Lyden D (2009) The metastatic niche: adapting the foreign soil. Nat Rev Cancer 9: 285-293
105. Hiratsuka S, Nakamura K, Iwai S, Murakami M, Itoh T, Kijima H, Shipley JM, Senior RM, Shibuya M (2002) MMP9 induction by vascular endothelial growth factor receptor-1 is involved in lung-specific metastasis. Cancer Cell 2: 289-300 (Pubitemid 41043963)
106. Dawson MR, Duda DG, Chae SS, Fukumura D, Jain RK (2009) VEGFR1 activity modulates myeloid cell infiltration in growing lung metastases but is not required for spontaneous metastasis formation. PLoS ONE 4: e6525
107. Iwakura Y, Ishigame H, Saijo S, Nakae S (2011) Functional specialization of interleukin-17 family members. Immunity 34: 149-162
108. Dunn L, Demichele A (2009) Genomic predictors of outcome and treatment response in breast cancer. Mol Diagn Ther 13: 73-90
109. Jung MY, Kim SH, Cho D, Kim TS (2009) Analysis of the expression profiles of cytokines and cytokine-related genes during the progression of breast cancer growth in mice. Oncol Rep 22: 1141-1147
110. Kolls JK, Linden A (2004) Interleukin-17 family members and inflammation. Immunity 21: 467-476 (Pubitemid 39370503)
111. Weaver CT, Hatton RD, Mangan PR, Harrington LE (2007) IL-17 family cytokines and the expanding diversity of effector T cell lineages. Annu Rev Immunol 25: 821-852 (Pubitemid 46697925)
112. Hirota K, Ahlfors H, Duarte JH, Stockinger B (2012) Regulation and function of innate and adaptive interleukin-17-producing cells. EMBO Rep 13: 113-120
113. Numasaki M, Fukushi J, Ono M, Narula SK, Zavodny PJ, Kudo T, Robbins PD, Tahara H, Lotze MT (2003) Interleukin-17 promotes angiogenesis and tumor growth. Blood 101: 2620-2627 (Pubitemid 36857622)
114. Tartour E et al (1999) Interleukin 17, a T-cell-derived cytokine, promotes tumorigenicity of human cervical tumors in nude mice. Cancer Res 59: 3698-3704 (Pubitemid 29381875)
115. Pelletier M et al (2010) Evidence for a cross-talk between human neutrophils and Th17 cells. Blood 115: 335-343
116. Iida T et al (2011) Tumor-infiltrating CD4+ Th17 cells produce IL-17 in tumor microenvironment and promote tumor progression in human gastric cancer. Oncol Rep 25: 1271-1277
117. Schnyder B, Schnyder-Candrian S, Pansky A, Schmitz ML, Heim M, Ryffel B, Moser R (2005) IL-17 reduces TNF-induced Rantes and VCAM-1 expression. Cytokine 31: 191-202 (Pubitemid 40967902)
118. Letuve S, Lajoie-Kadoch S, Audusseau S, Rothenberg ME, Fiset PO, Ludwig MS, Hamid Q (2006) IL-17E upregulates the expression of proinflammatory cytokines in lung fibroblasts. J Allergy Clin Immunol 117: 590-596 (Pubitemid 43340223)
119. Wang L, Yi T, Kortylewski M, Pardoll DM, Zeng D, Yu H (2009) IL-17 can promote tumor growth through an IL-6-Stat3 signaling pathway. J Exp Med 206: 1457-1464
120. Chae WJ, Gibson TF, Zelterman D, Hao L, Henegariu O, Bothwell AL (2010) Ablation of IL-17A abrogates progression of spontaneous intestinal tumorigenesis. Proc Natl Acad Sci USA 107: 5540-5544
121. Benatar T et al (2010) IL-17E, a proinflammatory cytokine, has antitumor efficacy against several tumor types in vivo. Cancer Immunol Immunother 59: 805-817
122. Zhang P, Ozdemir T, Chung CY, Robertson GP, Dong C (2011) Sequential binding of alphaVbeta3 and ICAM-1 determines fibrin-mediated melanoma capture and stable adhesion to CD11b/CD18 on neutrophils. J Immunol 186: 242-254
123. Li GC et al (2010) Human mesenchymal stem cells inhibit metastasis of a hepatocellular carcinoma model using the MHCC97-H cell line. Cancer Sci 101: 2546-2553
124. Uccelli A, Moretta L, Pistoia V (2006) Immunoregulatory function of mesenchymal stem cells. Eur J Immunol 36: 2566-2573 (Pubitemid 44608440)
125. Di Nicola M, Carlo-Stella C, Magni M, Milanesi M, Longoni PD, Matteucci P, Grisanti S, Gianni AM (2002) Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 99: 3838-3843 (Pubitemid 34534559)
126. Plumas J, Chaperot L, Richard MJ, Molens JP, Bensa JC, Favrot MC (2005) Mesenchymal stem cells induce apoptosis of activated T cells. Leukemia 19: 1597-1604 (Pubitemid 43090404)
127. Jiang XX, Zhang Y, Liu B, Zhang SX, Wu Y, Yu XD, Mao N (2005) Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells. Blood 105: 4120-4126 (Pubitemid 40656164)
128. Nauta AJ, Kruisselbrink AB, Lurvink E, Willemze R, Fibbe WE (2006) Mesenchymal stem cells inhibit generation and function of both CD34+-derived and monocyte-derived dendritic cells. J Immunol 177: 2080-2087 (Pubitemid 44200965)
129. Zhang W, Ge W, Li C, You S, Liao L, Han Q, Deng W, Zhao RC (2004) Effects of mesenchymal stem cells on differentiation, maturation, and function of human monocyte-derived dendritic cells. Stem Cells Dev 13: 263-271 (Pubitemid 38738368)
130. Corcione A et al (2006) Human mesenchymal stem cells modulate B-cell functions. Blood 107: 367-372 (Pubitemid 43053565)
131. Rutella S, Danese S, Leone G (2006) Tolerogenic dendritic cells: cytokine modulation comes of age. Blood 108: 1435-1440 (Pubitemid 44316106)
132. Selmani Z et al (2008) Human leukocyte antigen-G5 secretion by human mesenchymal stem cells is required to suppress T lymphocyte and natural killer function and to induce CD4+CD25highFOXP3+ regulatory T cells. Stem Cells 26: 212-222
133. Di Ianni M, Del Papa B, De Ioanni M, Moretti L, Bonifacio E, Cecchini D, Sportoletti P, Falzetti F, Tabilio A (2008) Mesenchymal cells recruit and regulate T regulatory cells. Exp Hematol 36: 309-318 (Pubitemid 351221170)
134. Aggarwal S, Pittenger MF (2005) Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 105: 1815-1822 (Pubitemid 40223708)
135. Djouad F, Bony C, Apparailly F, Louis-Plence P, Jorgensen C, Noel D (2006) Earlier onset of syngeneic tumors in the presence of mesenchymal stem cells. Transplantation 82: 1060-1066 (Pubitemid 44632122)
136. Patel SA, Meyer JR, Greco SJ, Corcoran KE, Bryan M, Rameshwar P (2010) Mesenchymal stem cells protect breast cancer cells through regulatory T cells: role of mesenchymal stem cell-derived TGF-beta. J Immunol 184: 5885-5894
137. Liao D, Luo Y, Markowitz D, Xiang R, Reisfeld RA (2009) Cancer associated fibroblasts promote tumor growth and metastasis by modulating the tumor immune microenvironment in a 4T1 murine breast cancer model. PLoS One 4: e7965
138. Schreiber RD, Old LJ, Smyth MJ (2011) Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion. Science 331: 1565-1570
139. Dighe AS, Richards E, Old LJ, Schreiber RD (1994) Enhanced in vivo growth and resistance to rejection of tumor cells expressing dominant negative IFN gamma receptors. Immunity 1: 447-456
140. Kaplan DH, Shankaran V, Dighe AS, Stockert E, Aguet M, Old LJ, Schreiber RD (1998) Demonstration of an interferon gamma-dependent tumor surveillance system in immunocompetent mice. Proc Natl Acad Sci USA 95: 7556-7561 (Pubitemid 28293291)
141. Shankaran V, Ikeda H, Bruce AT, White JM, Swanson PE, Old LJ, Schreiber RD (2001) IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature 410: 1107-1111 (Pubitemid 32391043)
142. Koebel CM, Vermi W, Swann JB, Zerafa N, Rodig SJ, Old LJ, Smyth MJ, Schreiber RD (2007) Adaptive immunity maintains occult cancer in an equilibrium state. Nature 450: 903-907 (Pubitemid 350231320)
143. de Visser KE, Korets LV, Coussens LM (2005) De novo carcinogenesis promoted by chronic inflammation is B lymphocyte dependent. Cancer Cell 7: 411-423 (Pubitemid 40719125)
144. DeNardo DG, Barreto JB, Andreu P, Vasquez L, Tawfik D, Kolhatkar N, Coussens LM (2009) CD4(+) T cells regulate pulmonary metastasis of mammary carcinomas by enhancing protumor properties of macrophages. Cancer Cell 16: 91-102
145. Liu F et al (2011) CD8(+) cytotoxic T cell and FOXP3(+) regulatory T cell infiltration in relation to breast cancer survival and molecular subtypes. Breast Cancer Res Treat, 10.1007/s10549-011-1647-3
146. Barnett JC et al (2010) Ovarian cancer tumor infiltrating T-regulatory (T(reg)) cells are associated with a metastatic phenotype. Gynecol Oncol 116: 556-562
147. Yang ZQ, Yang ZY, Zhang LD, Ping B, Wang SG, Ma KS, Li XW, Dong JH (2010) Increased liver-infiltrating CD8+FoxP3+ regulatory T cells are associated with tumor stage in hepatocellular carcinoma patients. Hum Immunol 71: 1180-1186
148. Curiel TJ (2008) Regulatory T cells and treatment of cancer. Curr Opin Immunol 20: 241-246
149. Mempel TR, Pittet MJ, Khazaie K, Weninger W, Weissleder R, von Boehmer H, von Andrian UH (2006) Regulatory T cells reversibly suppress cytotoxic T cell function independent of effector differentiation. Immunity 25: 129-141 (Pubitemid 44066829)
150. Shimizu J, Yamazaki S, Takahashi T, Ishida Y, Sakaguchi S (2002) Stimulation of CD25(+)CD4(+) regulatory T cells through GITR breaks immunological self-tolerance. Nat Immunol 3: 135-142 (Pubitemid 34141443)
151. Piccirillo CA, Shevach EM (2001) Cutting edge: control of CD8+ T cell activation by CD4+CD25+ immunoregulatory cells. J Immunol 167: 1137-1140 (Pubitemid 32703105)
152. Sather BD, Treuting P, Perdue N, Miazgowicz M, Fontenot JD, Rudensky AY, Campbell DJ (2007) Altering the distribution of Foxp3(+) regulatory T cells results in tissue-specific inflammatory disease. J Exp Med 204: 1335-1347 (Pubitemid 46919872)
153. Sakaguchi S, Yamaguchi T, Nomura T, Ono M (2008) Regulatory T cells and immune tolerance. Cell 133: 775-787 (Pubitemid 351707693)
154. Feuerer M, Hill JA, Mathis D, Benoist C (2009) Foxp3+ regulatory T cells: differentiation, specification, subphenotypes. Nat Immunol 10: 689-695
155. Lindley S, Dayan CM, Bishop A, Roep BO, Peakman M, Tree TI (2005) Defective suppressor function in CD4(+)CD25(+) T-cells from patients with type 1 diabetes. Diabetes 54: 92-99 (Pubitemid 40105099)
156. Ehrenstein MR, Evans JG, Singh A, Moore S, Warnes G, Isenberg DA, Mauri C (2004) Compromised function of regulatory T cells in rheumatoid arthritis and reversal by anti-TNFalpha therapy. J Exp Med 200: 277-285 (Pubitemid 39031247)
157. Horwitz DA (2008) Regulatory T cells in systemic lupus erythematosus: past, present and future. Arthritis Res Ther 10: 227
158. Josefowicz SZ, Rudensky A (2009) Control of regulatory T cell lineage commitment and maintenance. Immunity 30: 616-625
159. Fontenot JD, Gavin MA, Rudensky AY (2003) Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol 4: 330-336 (Pubitemid 36432314)
160. Hori S, Nomura T, Sakaguchi S (2003) Control of regulatory T cell development by the transcription factor Foxp3. Science 299: 1057-1061 (Pubitemid 36222930)
161. Bennett CL et al (2001) The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat Genet 27: 20-21 (Pubitemid 32044513)
162. Chatila TA, Blaeser F, Ho N, Lederman HM, Voulgaropoulos C, Helms C, Bowcock AM (2000) JM2, encoding a fork head-related protein, is mutated in X-linked autoimmunity-allergic disregulation syndrome. J Clin Invest 106: R75-81 (Pubitemid 32038594)
163. Hong H, Gu Y, Zhang H, Simon AK, Chen X, Wu C, Xu XN, Jiang S (2010) Depletion of CD4+CD25+ regulatory T cells enhances natural killer T cell-mediated anti-tumour immunity in a murine mammary breast cancer model. Clin Exp Immunol 159: 93-99
164. Onizuka S, Tawara I, Shimizu J, Sakaguchi S, Fujita T, Nakayama E (1999) Tumor rejection by in vivo administration of anti-CD25 (interleukin-2 receptor alpha) monoclonal antibody. Cancer Res 59: 3128-3133 (Pubitemid 29316012)
165. Teng MW, Ngiow SF, von Scheidt B, McLaughlin N, Sparwasser T, Smyth MJ (2010) Conditional regulatory T-cell depletion releases adaptive immunity preventing carcinogenesis and suppressing established tumor growth. Cancer Res 70: 7800-7809
166. Granville CA et al (2009) A central role for Foxp3+ regulatory T cells in K-Ras-driven lung tumorigenesis. PLoS One 4: e5061
167. Olkhanud PB et al (2009) Breast cancer lung metastasis requires expression of chemokine receptor CCR4 and regulatory T cells. Cancer Res 69: 5996-6004
168. Terabe M et al (2005) A nonclassical non-Valpha14Jalpha18 CD1d-restricted (type II) NKT cell is sufficient for down-regulation of tumor immunosurveillance. J Exp Med 202: 1627-1633 (Pubitemid 41815868)
169. Ostrand-Rosenberg S, Clements VK, Terabe M, Park JM, Berzofsky JA, Dissanayake SK (2002) Resistance to metastatic disease in STAT6-deficient mice requires hemopoietic and nonhemopoietic cells and is IFN-gamma dependent. J Immunol 169: 5796-5804 (Pubitemid 35291682)
170. Olkhanud PB, Damdinsuren B, Bodogai M, Gress RE, Sen R, Wejksza K, Malchinkhuu E, Wersto RP, Biragyn A (2011) Tumor-evoked regulatory B cells promote breast cancer metastasis by converting resting CD4 T cells to T-regulatory cells. Cancer Res 71: 3505-3515
171. Xu L, Xu W, Wen Z, Xiong S (2011) In situ prior proliferation of CD4+ CCR6+ regulatory T cells facilitated by TGF-beta secreting DCs is crucial for their enrichment and suppression in tumor immunity. PLoS ONE 6: e20282
172. Yang R, Cai Z, Zhang Y, Yutzy WHt, Roby KF, Roden RB (2006) CD80 in immune suppression by mouse ovarian carcinoma-associated Gr-1+CD11b+ myeloid cells. Cancer Res 66: 6807-6815 (Pubitemid 44085641)
173. Huang B, Pan PY, Li Q, Sato AI, Levy DE, Bromberg J, Divino CM, Chen SH (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: 1123-1131 (Pubitemid 43165981)
174. Khalkhali-Ellis Z (2006) Maspin: the new frontier. Clin Cancer Res 12: 7279-7283 (Pubitemid 46095399)
175. Shi HY, Zhang W, Liang R, Abraham S, Kittrell FS, Medina D, Zhang M (2001) Blocking tumor growth, invasion, and metastasis by maspin in a syngeneic breast cancer model. Cancer Res 61: 6945-6951 (Pubitemid 32896523)
176. Zou Z, Anisowicz A, Hendrix MJ, Thor A, Neveu M, Sheng S, Rafidi K, Seftor E, Sager R (1994) Maspin, a serpin with tumor-suppressing activity in human mammary epithelial cells. Science 263: 526-529 (Pubitemid 24082753)
177. Gilbert LA, Hemann MT (2010) DNA damage-mediated induction of a chemoresistant niche. Cell 143: 355-366
178. Kidd S et al (2009) Direct evidence of mesenchymal stem cell tropism for tumor and wounding microenvironments using in vivo bioluminescent imaging. Stem Cells 27: 2614-2623
179. Nakamizo A et al (2005) Human bone marrow-derived mesenchymal stem cells in the treatment of gliomas. Cancer Res 65: 3307-3318 (Pubitemid 40524615)
180. Studeny M, Marini FC, Dembinski JL, Zompetta C, Cabreira-Hansen M, Bekele BN, Champlin RE, Andreeff M (2004) Mesenchymal stem cells: potential precursors for tumor stroma and targeted-delivery vehicles for anticancer agents. J Natl Cancer Inst 96: 1593-1603 (Pubitemid 39534883)
181. Komarova S, Kawakami Y, Stoff-Khalili MA, Curiel DT, Pereboeva L (2006) Mesenchymal progenitor cells as cellular vehicles for delivery of oncolytic adenoviruses. Mol Cancer Ther 5: 755-766
182. Ren C, Kumar S, Chanda D, Chen J, Mountz JD, Ponnazhagan S (2008) Therapeutic potential of mesenchymal stem cells producing interferon-alpha in a mouse melanoma lung metastasis model. Stem Cells 26: 2332-2338
183. Chen X et al (2008) A tumor-selective biotherapy with prolonged impact on established metastases based on cytokine gene-engineered MSCs. Mol Ther 16: 749-756 (Pubitemid 351426177)
184. Loebinger MR, Eddaoudi A, Davies D, Janes SM (2009) Mesenchymal stem cell delivery of TRAIL can eliminate metastatic cancer. Cancer Res 69: 4134-4142
185. Mohr A, Albarenque SM, Deedigan L, Yu R, Reidy M, Fulda S, Zwacka RM (2010) Targeting of XIAP combined with systemic mesenchymal stem cell-mediated delivery of sTRAIL ligand inhibits metastatic growth of pancreatic carcinoma cells. Stem Cells 28: 2109-2120
186. Wiley SR et al (1995) Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity 3: 673-682
187. Walczak H et al (1999) Tumoricidal activity of tumor necrosis factor-related apoptosis-inducing ligand in vivo. Nat Med 5: 157-163 (Pubitemid 29068521)
188. Ashkenazi A et al (1999) Safety and antitumor activity of recombinant soluble Apo2 ligand. J Clin Invest 104: 155-162
189. Sasportas LS et al (2009) Assessment of therapeutic efficacy and fate of engineered human mesenchymal stem cells for cancer therapy. Proc Natl Acad Sci USA 106: 4822-4827
190. Studeny M, Marini FC, Champlin RE, Zompetta C, Fidler IJ, Andreeff M (2002) Bone marrow-derived mesenchymal stem cells as vehicles for interferon-beta delivery into tumors. Cancer Res 62: 3603-3608 (Pubitemid 34728832)
191. Baggiolini M (1998) Chemokines and leukocyte traffic. Nature 392: 565-568 (Pubitemid 28207705)
192. Lee JS, Hong JM, Moon GJ, Lee PH, Ahn YH, Bang OY (2010) A long-term follow-up study of intravenous autologous mesenchymal stem cell transplantation in patients with ischemic stroke. Stem Cells 28: 1099-1106
193. Karussis D et al (2010) Safety and immunological effects of mesenchymal stem cell transplantation in patients with multiple sclerosis and amyotrophic lateral sclerosis. Arch Neurol 67: 1187-1194
194. Macmillan ML, Blazar BR, DeFor TE, Wagner JE (2009) Transplantation of ex-vivo culture-expanded parental haploidentical mesenchymal stem cells to promote engraftment in pediatric recipients of unrelated donor umbilical cord blood: results of a phase I-II clinical trial. Bone Marrow Transplant 43: 447-454
195. Quarto R, Mastrogiacomo M, Cancedda R, Kutepov SM, Mukhachev V, Lavroukov A, Kon E, Marcacci M (2001) Repair of large bone defects with the use of autologous bone marrow stromal cells. N Engl J Med 344: 385-386 (Pubitemid 32107654)
196. Marcacci M, Kon E, Moukhachev V, Lavroukov A, Kutepov S, Quarto R, Mastrogiacomo M, Cancedda R (2007) Stem cells associated with macroporous bioceramics for long bone repair: 6-to 7-year outcome of a pilot clinical study. Tissue Eng 13: 947-955 (Pubitemid 46870419)
197. Perrone G et al (2008) Intratumoural FOXP3-positive regulatory T cells are associated with adverse prognosis in radically resected gastric cancer. Eur J Cancer 44: 1875-1882
198. Merlo A, Casalini P, Carcangiu ML, Malventano C, Triulzi T, Menard S, Tagliabue E, Balsari A (2009) FOXP3 expression and overall survival in breast cancer. J Clin Oncol 27: 1746-1752
199. Nakamura R et al (2009) Accumulation of regulatory T cells in sentinel lymph nodes is a prognostic predictor in patients with node-negative breast cancer. Eur J Cancer 45: 2123-2131
200. French JD, Weber ZJ, Fretwell DL, Said S, Klopper JP, Haugen BR (2010) Tumor-associated lymphocytes and increased FoxP3+ regulatory T cell frequency correlate with more aggressive papillary thyroid cancer. J Clin Endocrinol Metab 95: 2325-2333
201. Klages K et al (2010) Selective depletion of Foxp3+ regulatory T cells improves effective therapeutic vaccination against established melanoma. Cancer Res 70: 7788-7799
202. Jacobs JF et al (2010) Dendritic cell vaccination in combination with anti-CD25 monoclonal antibody treatment: a phase I/II study in metastatic melanoma patients. Clin Cancer Res 16: 5067-5078
203. Dannull J et al (2005) Enhancement of vaccine-mediated antitumor immunity in cancer patients after depletion of regulatory T cells. J Clin Invest 115: 3623-3633 (Pubitemid 43121851)
204. Stewart TJ, Smyth MJ (2011) Improving cancer immunotherapy by targeting tumor-induced immune suppression. Cancer Metastasis Rev 30: 125-140