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Cited by 280Immune cells in cancerSarcoma Diagnosis and TreatmentCancer Cells and Metastasis

Tumor-Associated Macrophages in Osteosarcoma: From Mechanisms to Therapy

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Cersosimo, Francesca, Lonardi, Silvia, Bernardini, Giulia, Telfer, Brian, Mandelli, Giulio Eugenio, Santucci, Annalisa, Vermi, William, Giurisato, Emanuele·2020·International Journal of Molecular Sciences
DOI 10.3390/ijms21155207PMC PMC7432207
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Abstract

Osteosarcomas (OSs) are bone tumors most commonly found in pediatric and adolescent patients characterized by high risk of metastatic progression and recurrence after therapy. Effective therapeutic management of this disease still remains elusive as evidenced by poor patient survival rates. To achieve a more effective therapeutic management regimen, and hence patient survival, there is a need to identify more focused targeted therapies for OSs treatment in the clinical setting. The role of the OS tumor stroma microenvironment plays a significant part in the development and dissemination of this disease. Important components, and hence potential targets for treatment, are the tumor-infiltrating macrophages that are known to orchestrate many aspects of OS stromal signaling and disease progression. In particular, increased infiltration of M2-like tumor-associated macrophages (TAMs) has been associated with OS metastasis and poor patient prognosis despite currently used aggressive therapies regimens. This review aims to provide a summary update of current macrophage-centered knowledge and to discuss the possible roles that macrophages play in the process of OS metastasis development focusing on the potential influence of stromal cross-talk signaling between TAMs, cancer-stem cells and additional OSs tumoral microenvironment factors.

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  1. [1]Nie Z. Peng H. Osteosarcoma in patients below 25 years of age: An observational study of incidence, metastasis, treatment and outcomes Oncol. Lett. 2018 16 6502 6514 10.3892/ol.2018.9453 30405789 PMC6202522 · DOI
  2. [2]Zhang B. Zhang Y. Li R. Li J. Lu X. Zhang Y. The efficacy and safety comparison of first-line chemotherapeutic agents (high-dose methotrexate, doxorubicin, cisplatin, and ifosfamide) for osteosarcoma: A network meta-analysis J. Orthop. Surg. Res. 2020 15 51 10.1186/s13018-020-1576-0 32054494 PMC7020590 · DOI
  3. [4]Buddingh E.P. Kuijjer M.L. Duim R.A. Bürger H. Agelopoulos K. Myklebost O. Serra M. Mertens F. Hogendoorn P.C. Lankester A.C. Tumor-infiltrating macrophages are associated with metastasis suppression in high-grade osteosarcoma: A rationale for treatment with macrophage activating agents Clin. Cancer Res. 2011 17 2110 2119 10.1158/1078-0432.CCR-10-2047 21372215 · DOI · Paper page
  4. [5]Han Y. Guo W. Ren T. Huang Y. Wang S. Liu K. Zheng B. Yang K. Zhang H. Liang X. Tumor-associated macrophages promote lung metastasis and induce epithelial-mesenchymal transition in osteosarcoma by activating the COX-2/STAT3 axis Cancer Lett. 2019 440–441 116 125 10.1016/j.canlet.2018.10.011 30343113 · DOI
  5. [6]Dumars C. Ngyuen J.M. Gaultier A. Lanel R. Corradini N. Gouin F. Heymann D. Heymann M.F. Dysregulation of macrophage polarization is associated with the metastatic process in osteosarcoma Oncotarget 2016 7 78343 78354 10.18632/oncotarget.13055 27823976 PMC5346643 · DOI
  6. [7]Ségaliny A.I. Mohamadia A. Dizier B. Lokajczyk A. Brion R. Lanel R. Amiaud J. Charrier C. Boisson-Vidal C. Heymann D. Interleukin-34 promotes tumor progression and metastatic process in osteosarcoma through induction of angiogenesis and macrophage recruitment Int. J. Cancer 2015 137 73 85 10.1002/ijc.29376 25471534 · DOI · Paper page
  7. [8]Zhou Q. Xian M. Xiang S. Xiang D. Shao X. Wang J. Cao J. Yang X. Yang B. Ying M. All-Trans Retinoic Acid Prevents Osteosarcoma Metastasis by Inhibiting M2 Polarization of Tumor-Associated Macrophages Cancer Immunol. Res. 2017 5 547 559 10.1158/2326-6066.CIR-16-0259 28515123 · DOI
  8. [9]Ottaviani G. Jaffe N. The epidemiology of osteosarcoma Cancer Treat. Res. 2009 152 3 13 10.1007/978-1-4419-0284-9_1 20213383 · DOI
  9. [10]Gonzalez A.L. Cates J.M.M. Osteosarcoma: Differential Diagnostic Considerations Surg. Pathol. Clin. 2012 5 117 146 10.1016/j.path.2011.07.011 26837918 · DOI
  10. [11]Nouri H. Maitigue M.B. Abid L. Nouri N. Abdelkader A. Bouaziz M. Mestiri M. Surface osteosarcoma: Clinical features and therapeutic implications J. Bone Oncol. 2015 4 115 123 10.1016/j.jbo.2015.07.002 26730360 PMC4678793 · DOI
  11. [12]Angelini A. Mavrogenis A.F. Trovarelli G. Ferrari S. Picci P. Ruggieri P. Telangiectatic osteosarcoma: A review of 87 cases J. Cancer Res. Clin. Oncol. 2016 142 2197 2207 10.1007/s00432-016-2210-8 27469493 PMC11819139 · DOI
  12. [13]Laschi M. Bernardini G. Geminiani M. Ghezzi L. Amato L. Braconi D. Millucci L. Frediani B. Spreafico A. Franchi A. Establishment of Four New Human Primary Cell Cultures from Chemo-Naïve Italian Osteosarcoma Patients J. Cell Physiol. 2015 230 2718 2727 10.1002/jcp.24996 25809010 · DOI
  13. [14]Rickel K. Fang F. Tao J. Molecular genetics of osteosarcoma Bone 2017 102 69 79 10.1016/j.bone.2016.10.017 27760307 PMC5393957 · DOI
  14. [15]Gianferante D.M. Mirabello L. Savage S.A. Germline and somatic genetics of osteosarcoma—Connecting aetiology, biology and therapy Nat. Rev. Endocrinol. 2017 13 480 491 10.1038/nrendo.2017.16 28338660 · DOI
  15. [16]Mirabello L. Zhu B. Koster R. Karlins E. Dean M. Yeager M. Gianferante M. Spector L.G. Morton L.M. Karyadi D. Frequency of Pathogenic Germline Variants in Cancer-Susceptibility Genes in Patients with Osteosarcoma JAMA Oncol. 2020 10.1001/jamaoncol.2020.0197 PMC7082769 32191290 · DOI · Paper page
  16. [17]Perry J.A. Kiezun A. Tonzi P. Van Allen E.M. Carter S.L. Baca S.C. Cowley G.S. Bhatt A.S. Rheinbay E. Pedamallu C.S. Complementary genomic approaches highlight the PI3K/mTOR pathway as a common vulnerability in osteosarcoma Proc. Natl. Acad. Sci. USA 2014 111 E5564 E5573 10.1073/pnas.1419260111 25512523 PMC4280630 · DOI · Paper page
  17. [19]Vogelstein B. Papadopoulos N. Velculescu V.E. Zhou S. Diaz L.A. Jr. Kinzler K.W. Cancer genome landscapes Science 2013 339 1546 1558 10.1126/science.1235122 23539594 PMC3749880 · DOI · Paper page
  18. [20]Velletri T. Xie N. Wang Y. Huang Y. Yang Q. Chen X. Chen Q. Shou P. Gan Y. Cao G. P53 functional abnormality in mesenchymal stem cells promotes osteosarcoma development Cell Death Dis. 2016 7 e2015 10.1038/cddis.2015.367 26775693 PMC4816167 · DOI
  19. [21]Franceschini N. Lam S.W. Cleton-Jansen A.M. Bovée J.V.M.G. What’s new in bone forming tumours of the skeleton? Virchows Arch. 2020 476 147 157 10.1007/s00428-019-02683-w 31741049 PMC6969005 · DOI
  20. [22]Tian W. Li Y. Zhang J. Li J. Gao J. Combined analysis of DNA methylation and gene expression profiles of osteosarcoma identified several prognosis signatures Gene 2018 650 7 14 10.1016/j.gene.2018.01.093 29407229 · DOI
  21. [23]Guo X. Liu W. Pan Y. Ni P. Ji J. Guo L. Zhang J. Wu J. Jiang J. Chen X. Homeobox gene IRX1 is a tumor suppressor gene in gastric carcinoma Oncogene 2010 29 3908 3920 10.1038/onc.2010.143 20440264 · DOI
  22. [24]Moriarity B.S. Otto G.M. Rahmann E.P. Rathe S.K. Wolf N.K. Weg M.T. Manlove L.A. LaRue R.S. Temiz N.A. Molyneux S.D. A Sleeping Beauty forward genetic screen identifies new genes and pathways driving osteosarcoma development and metastasis Nat. Genet. 2015 47 615 624 10.1038/ng.3293 25961939 PMC4767150 · DOI
  23. [25]Rosenblum J.M. Wijetunga N.A. Fazzari M.J. Krailo M. Barkauskas D.A. Gorlick R. Greally J.M. Predictive properties of DNA methylation patterns in primary tumor samples for osteosarcoma relapse status Epigenetics 2015 10 31 39 10.4161/15592294.2014.989084 25531418 PMC4622015 · DOI
  24. [26]Zhou W. Hao M. Du X. Chen K. Wang G. Yang J. Advances in targeted therapy for osteosarcoma Discov. Med. 2014 17 301 307 24979249
  25. [27]Zhang J. Yu X.H. Yan Y.G. Wang C. Wang W.J. PI3K/Akt signaling in osteosarcoma Clin. Chim. Acta 2015 444 182 192 10.1016/j.cca.2014.12.041 25704303 · DOI
  26. [28]Chen C. Zhao M. Tian A. Zhang X. Yao Z. Ma X. Aberrant activation of Wnt/β-catenin signaling drives proliferation of bone sarcoma cells Oncotarget 2015 6 17570 17583 10.18632/oncotarget.4100 25999350 PMC4627329 · DOI
  27. [29]Cai Z. Cao Y. Luo Y. Hu H. Ling H. Signalling mechanism(s) of epithelial-mesenchymal transition and cancer stem cells in tumour therapeutic resistance Clin. Chim. Acta 2018 483 156 163 10.1016/j.cca.2018.04.033 29709449 · DOI
  28. [30]Iwaya K. Ogawa H. Kuroda M. Izumi M. Ishida T. Mukai K. Cytoplasmic and/or nuclear staining of beta-catenin is associated with lung metastasis Clin. Exp. Metastasis 2003 20 525 529 10.1023/A:1025821229013 14598886 · DOI
  29. [32]Luke J.J. Bao R. Sweis R.F. Spranger S. Gajewski T.F. WNT/β-catenin Pathway Activation Correlates with Immune Exclusion across Human Cancers Clin. Cancer Res. 2019 25 3074 3083 10.1158/1078-0432.CCR-18-1942 30635339 PMC6522301 · DOI · Paper page
  30. [33]Hirotsu M. Setoguchi T. Sasaki H. Matsunoshita Y. Gao H. Nagao H. Kunigou O. Komiya S. Smoothened as a new therapeutic target for human osteosarcoma Mol. Cancer 2010 9 5 10.1186/1476-4598-9-5 20067614 PMC2818696 · DOI
  31. [34]Lo W.W. Pinnaduwage D. Gokgoz N. Wunder J.S. Andrulis I.L. Aberrant hedgehog signaling and clinical outcome in osteosarcoma Sarcoma 2014 2014 261804 10.1155/2014/261804 24799831 PMC3985328 · DOI
  32. [35]Bernardini G. Geminiani M. Gambassi S. Orlandini M. Petricci E. Marzocchi B. Laschi M. Taddei M. Manetti F. Santucci A. Novel smoothened antagonists as anti-neoplastic agents for the treatment of osteosarcoma J. Cell. Physiol. 2018 233 4961 4971 10.1002/jcp.26330 29215700 · DOI
  33. [36]Lo W.W. Wunder J.S. Dickson B.C. Campbell V. McGovern K. Alman B.A. Andrulis I.L. Involvement and targeted intervention of dysregulated Hedgehog signaling in osteosarcoma Cancer 2014 120 537 547 10.1002/cncr.28439 24151134 · DOI
  34. [37]Righi A. Gambarotti M. Sbaraglia M. Sisto A. Ferrari S. Dei Tos A.P. Picci P. P16 Expression as a Prognostic and Predictive Marker in High-Grade Localized Osteosarcoma of the Extremities: An Analysis of 357 Cases Hum. Pathol. 2016 58 15 23 10.1016/j.humpath.2016.07.023 27544803 · DOI
  35. [38]Abdou A.G. Kandil M. Asaad N.Y. Dawoud M.M. Shahin A.A. Abd Eldayem A.F. The prognostic role of Ezrin and HER2/neu expression in osteosarcoma Appl. Immunohistochem. Mol. Morphol. 2016 24 355 363 10.1097/PAI.0000000000000197 26067138 · DOI
  36. [39]Xie X. Li Y. Zhu H. Kuang Z. Chen D. Fan T. Prognostic Significance of β-Catenin Expression in Osteosarcoma: A Meta-Analysis Front. Oncol. 2020 10 402 10.3389/fonc.2020.00402 32328456 PMC7160797 · DOI
  37. [40]Corre I. Verrecchia F. Crenn V. Redini F. Trichet V. The Osteosarcoma Microenvironment: A Complex but Targetable Ecosystem Cells 2020 9 976 10.3390/cells9040976 32326444 PMC7226971 · DOI
  38. [41]Giurisato E. Xu Q. Lonardi S. Telfer B. Russo I. Pearson A. Finegan K.G. Wang W. Wang J. Gray N.S. Myeloid ERK5 deficiency suppresses tumor growth by blocking protumor macrophage polarization via STAT3 inhibition Proc. Natl. Acad. Sci. USA 2018 115 E2801 E2810 10.1073/pnas.1707929115 29507229 PMC5866536 · DOI
  39. [42]Gordon S. Plüddemann A. Martinez Estrada F. Macrophage heterogeneity in tissues: Phenotypic diversity and functions Immunol. Rev. 2014 262 36 55 10.1111/imr.12223 25319326 PMC4231239 · DOI
  40. [43]Pollard J.W. Trophic macrophages in development and disease Nat. Rev. Immunol. 2009 9 259 270 10.1038/nri2528 19282852 PMC3648866 · DOI · Paper page
  41. [44]Mukhopadhyay S. Plüddemann A. Gordon S. Macrophage pattern recognition receptors in immunity, homeostasis and self tolerance Adv. Exp. Med. Biol. 2009 653 1 14 10.1007/978-1-4419-0901-5_1 19799108 PMC7123833 · DOI
  42. [45]Aderem A. Phagocytosis and the inflammatory response J. Infect. Dis. 2003 187 Suppl. 2 S340 S345 10.1086/374747 12792849 · DOI
  43. [46]Tsukasaki M. Takayanagi H. Osteoimmunology: Evolving concepts in bone-immune interactions in health and disease Nat. Rev. Immunol. 2019 19 626 642 10.1038/s41577-019-0178-8 31186549 · DOI
  44. [47]Chang M.K. Raggatt L.J. Alexander K.A. Kuliwaba J.S. Fazzalari N.L. Schroder K. Maylin E.R. Ripoll V.M. Hume D.A. Pettit A.R. Osteal tissue macrophages are intercalated throughout human and mouse bone lining tissues and regulate osteoblast function in vitro and in vivo J. Immunol. 2008 181 1232 1244 10.4049/jimmunol.181.2.1232 18606677 · DOI
  45. [48]Champagne C.M. Takebe J. Offenbacher S. Cooper L.F. Macrophage cell lines produce osteoinductive signals that include bone morphogenetic protein-2 Bone 2002 30 26 31 10.1016/S8756-3282(01)00638-X 11792561 · DOI
  46. [49]Nicolaidou V. Wong M.M. Redpath A.N. Ersek A. Baban D.F. Williams L.M. Cope A.P. Horwood N.J. Monocytes induce STAT3 activation in human mesenchymal stem cells to promote osteoblast formation PLoS ONE 2012 7 e39871 10.1371/journal.pone.0039871 22802946 PMC3389003 · DOI
  47. [50]Fernandes T.J. Hodge J.M. Singh P.P. Eeles D.G. Collier F.M. Holten I. Ebeling P.R. Nicholson G.C. Quinn J.M. Cord blood-derived macrophage-lineage cells rapidly stimulate osteoblastic maturation in mesenchymal stem cells in a glycoprotein-130 dependent manner PLoS ONE 2013 8 e73266 10.1371/journal.pone.0073266 24069182 PMC3772005 · DOI
  48. [51]Guihard P. Danger Y. Brounais B. David E. Brion R. Delecrin J. Richards C.D. Chevalier S. Rédini F. Heymann D. Induction of osteogenesis in mesenchymal stem cells by activated monocytes/macrophages depends on oncostatin M signaling Stem Cells 2012 30 762 772 10.1002/stem.1040 22267310 · DOI
  49. [52]Burnett S.H. Beus B.J. Avdiushko R. Qualls J. Kaplan A.M. Cohen D.A. Development of peritoneal adhesions in macrophage depleted mice J. Surg. Res. 2006 131 296 301 10.1016/j.jss.2005.08.026 16289593 · DOI
  50. [54]Vi L. Baht G.S. Whetstone H. Ng A. Wei Q. Poon R. Mylvaganam S. Grynpas M. Alman B.A. Macrophages promote osteoblastic differentiation in-vivo: Implications in fracture repair and bone homeostasis J. Bone Miner. Res. 2015 30 1090 1102 10.1002/jbmr.2422 25487241 · DOI · Paper page
  51. [55]Cho S.W. Soki F.N. Koh A.J. Eber M.R. Entezami P. Park S.I. van Rooijen N. McCauley L.K. Osteal macrophages support physiologic skeletal remodeling and anabolic actions of parathyroid hormone in bone PNAS 2014 111 1545 1550 10.1073/pnas.1315153111 24406853 PMC3910564 · DOI
  52. [56]Winkler I.G. Sims N.A. Pettit A.R. Barbier V. Nowlan B. Helwani F. Poulton I.J. van Rooijen N. Alexander K.A. Raggatt L.J. Bone marrow macrophages maintain hematopoietic stem cell (HSC) niches and their depletion mobilizes HSCs Blood 2010 116 4815 4828 10.1182/blood-2009-11-253534 20713966 · DOI · Paper page
  53. [57]Sica A. Mantovani A. Macrophage plasticity and polarization: In vivo veritas J. Clin. Investig. 2012 122 787 795 10.1172/JCI59643 22378047 PMC3287223 · DOI · Paper page
  54. [58]Martinez F.O. Regulators of macrophage activation Eur. J. Immunol. 2011 41 1531 1534 10.1002/eji.201141670 21607943 · DOI
  55. [59]Mantovani A. Sozzani S. Locati M. Allavena P. Sica A. Macrophage polarization: Tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes Trends Immunol. 2002 23 549 555 10.1016/S1471-4906(02)02302-5 12401408 · DOI · Paper page
  56. [61]Van Furth R. Cohn Z.A. The origin and kinetics of mononuclear phagocytes J. Exp. Med. 1968 128 415 435 10.1084/jem.128.3.415 5666958 PMC2138527 · DOI
  57. [62]Sawyer R.T. Strausbauch P.H. Volkman A. Resident macrophage proliferation in mice depleted of blood monocytes by strontium-89 Lab. Investig. 1982 46 165 170 6174824
  58. [66]Guilliams M. De Kleer I. Henri S. Post S. Vanhoutte L. De Prijck S. Deswarte K. Malissen B. Hammad H. Lambrecht B.N. Alveolar macrophages develop from fetal monocytes that differentiate into long-lived cells in the first week of life via GM-CSF J. Exp. Med. 2013 210 1977 1992 10.1084/jem.20131199 24043763 PMC3782041 · DOI
  59. [67]Jakubzick C. Gautier E.L. Gibbings S.L. Sojka D.K. Schlitzer A. Johnson T.E. Ivanov S. Duan Q. Bala S. Condon T. Minimal differentiation of classical monocytes as they survey steady-state tissues and transport antigen to lymph nodes Immunity 2013 39 599 610 10.1016/j.immuni.2013.08.007 24012416 PMC3820017 · DOI
  60. [69]Perdiguero E.G. Geissmann F. The development and maintenance of resident macrophages Nat. Immunol. 2016 17 2 8 10.1038/ni.3341 26681456 PMC4950995 · DOI
  61. [72]Mass E. Ballesteros I. Farlik M. Halbritter F. Günther P. Crozet L. Jacome-Galarza C.E. Händler K. Klughammer J. Kobayashi Y. Specification of tissue-resident macrophages during organogenesis Science 2016 353 aaf4238 10.1126/science.aaf4238 27492475 PMC5066309 · DOI · Paper page
  62. [74]Cecchini M.G. Dominguez M.G. Mocci S. Wetterwald A. Felix R. Fleisch H. Chisholm O. Hofstetter W. Pollard J.W. Stanley E.R. Role of colony stimulating factor-1 in the establishment and regulation of tissue macrophages during postnatal development of the mouse Development 1994 120 1357 1372 8050349
  63. [75]Martinez F.O. Gordon S. The M1 and M2 paradigm of macrophage activation: Time for reassessment F1000Prime Rep. 2014 6 13 10.12703/P6-13 24669294 PMC3944738 · DOI · Paper page
  64. [77]Martinez F.O. Sica A. Mantovani A. Locati M. Macrophage activation and polarization Front. Biosci. 2008 13 453 461 10.2741/2692 17981560 · DOI · Paper page
  65. [80]Biswas S.K. Mantovani A. Macrophage plasticity and interaction with lymphocyte subsets: Cancer as a paradigm Nat. Immunol. 2010 11 889 896 10.1038/ni.1937 20856220 · DOI · Paper page
  66. [81]Duluc D. Delneste Y. Tan F. Moles M.P. Grimaud L. Lenoir J. Preisser L. Anegon I. Catala L. Ifrah N. Tumor-associated leukemia inhibitory factor and IL-6 skew monocyte differentiation into tumor-associated macrophage-like cells Blood 2007 110 4319 4330 10.1182/blood-2007-02-072587 17848619 · DOI
  67. [82]Bingle L. Brown N.J. Lewis C.E. The role of tumour-associated macrophages in tumour progression: Implications for new anticancer therapies J. Pathol. 2002 196 254 265 10.1002/path.1027 11857487 · DOI · Paper page
  68. [83]Franklin R.A. Liao W. Sarkar A. Kim M.V. Bivona M.R. Liu K. Pamer E.G. Li M.O. The cellular and molecular origin of tumor-associated macrophages Science 2014 344 921 925 10.1126/science.1252510 24812208 PMC4204732 · DOI
  69. [84]Bottazzi B. Erba E. Nobili N. Fazioli F. Rambaldi A. Mantovani A. A paracrine circuit in the regulation of the proliferation of macrophages infiltrating murine sarcomas J. Immunol. 1990 144 2409 2412 2138198
  70. [85]Joyce J.A. Pollard J.W. Microenvironmental regulation of metastasis Nat. Rev. Cancer 2009 9 239 252 10.1038/nrc2618 19279573 PMC3251309 · DOI · Paper page
  71. [86]Wyckoff J.B. Wang Y. Lin E.Y. Li J.F. Goswami S. Stanley E.R. Segall J.E. Pollard J.W. Condeelis J. Direct visualization of macrophage-assisted tumor cell intravasation in mammary tumors Cancer Res. 2007 67 2649 2656 10.1158/0008-5472.CAN-06-1823 17363585 · DOI
  72. [87]Condeelis J. Pollard J.W. Macrophages: Obligate partners for tumor cell migration, invasion, and metastasis Cell 2006 124 263 266 10.1016/j.cell.2006.01.007 16439202 · DOI
  73. [88]Harney A.S. Arwert E.N. Entenberg D. Wang Y. Guo P. Qian B.Z. Oktay M.H. Pollard J.W. Jones J.G. Condeelis J.S. Real-Time Imaging Reveals Local, Transient Vascular Permeability, and Tumor Cell Intravasation Stimulated by TIE2hi Macrophage-Derived VEGFA Cancer Discov. 2015 5 932 943 10.1158/2159-8290.CD-15-0012 26269515 PMC4560669 · DOI
  74. [89]Frankenberger C. Rabe D. Bainer R. Sankarasharma D. Chada K. Krausz T. Gilad Y. Becker L. Rosner M.R. Metastasis Suppressors Regulate the Tumor Microenvironment by Blocking Recruitment of Prometastatic Tumor-Associated Macrophages Cancer Res. 2015 75 4063 4073 10.1158/0008-5472.CAN-14-3394 26238785 PMC4592465 · DOI
  75. [90]Terabe M. Matsui S. Park J.M. Mamura M. Noben-Trauth N. Donaldson D.D. Chen W. Wahl S.M. Ledbetter S. Pratt B. Transforming growth factor-beta production and myeloid cells are an effector mechanism through which CD1d-restricted T cells block cytotoxic T lymphocyte-mediated tumor immunosurveillance: Abrogation prevents tumor recurrence J. Exp. Med. 2003 198 1741 1752 10.1084/jem.20022227 14657224 PMC2194133 · DOI
  76. [91]Zea A.H. Rodriguez P.C. Atkins M.B. Hernandez C. Signoretti S. Zabaleta J. McDermott D. Quiceno D. Youmans A. O’Neill A. Arginase-producing myeloid suppressor cells in renal cell carcinoma patients: A mechanism of tumor evasion Cancer Res. 2005 65 3044 3048 10.1158/0008-5472.CAN-04-4505 15833831 · DOI
  77. [92]Sica A. Bronte V. Altered macrophage differentiation and immune dysfunction in tumor development J. Clin. Investig. 2007 117 1155 1166 10.1172/JCI31422 17476345 PMC1857267 · DOI
  78. [93]Munder M. Eichmann K. Modolell M. Alternative metabolic states in murine macrophages reflected by the nitric oxide synthase/arginase balance: Competitive regulation by CD4+ T cells correlates with Th1/Th2 phenotype J. Immunol. 1998 160 5347 5354 9605134
  79. [94]Chen L. Li J. Wang F. Dai C. Wu F. Liu X. Li T. Glauben R. Zhang Y. Nie G. Tie2 Expression on Macrophages Is Required for Blood Vessel Reconstruction and Tumor Relapse after Chemotherapy Cancer Res. 2016 76 6828 6838 10.1158/0008-5472.CAN-16-1114 27758887 · DOI
  80. [95]Pucci F. Venneri M.A. Biziato D. Nonis A. Moi D. Sica A. Di Serio C. Naldini L. Di Palma M. A distinguishing gene signature shared by tumor-infiltrating Tie2-expressing monocytes, blood “resident” monocytes, and embryonic macrophages suggests common functions and developmental relationships Blood 2009 114 901 914 10.1182/blood-2009-01-200931 19383967 · DOI
  81. [96]Liang X. Guo W. Ren T. Huang Y. Sun K. Zhang H. Yu Y. Wang W. Niu J. Macrophages reduce the sensitivity of osteosarcoma to neoadjuvant chemotherapy drugs by secreting Interleukin-1 beta Cancer Lett. 2020 480 4 14 10.1016/j.canlet.2020.03.019 32220541 · DOI
  82. [97]Han Q. Shi H. Liu F. CD163(+) M2-type tumor-associated macrophage support the suppression of tumor-infiltrating T cells in osteosarcoma Int. Immunopharmacol. 2016 34 101 106 10.1016/j.intimp.2016.01.023 26938675 · DOI
  83. [98]Su Y. Zhou Y. Sun Y.J. Wang Y.L. Yin J.Y. Huang Y.J. Zhang J.J. He A.N. Han K. Zhang H.Z. Macrophage-derived CCL18 promotes osteosarcoma proliferation and migration by upregulating the expression of UCA1 J. Mol. Med. 2019 97 49 61 10.1007/s00109-018-1711-0 30426155 · DOI
  84. [99]Shao X.J. Xiang S.F. Chen Y.Q. Zhang N. Cao J. Zhu H. Yang B. Zhou Q. Ying M.D. He Q.J. Inhibition of M2-like macrophages by all-trans retinoic acid prevents cancer initiation and stemness in osteosarcoma cells Acta Pharmacol. Sin. 2019 40 1343 1350 10.1038/s41401-019-0262-4 31296953 PMC6786412 · DOI
  85. [100]Jia X.H. Feng G.W. Wang Z.L. Du Y. Shen C. Hui H. Peng D. Li Z.J. Kong D.L. Tian J. Activation of mesenchymal stem cells by macrophages promotes tumor progression through immune suppressive effects Oncotarget 2016 7 20934 20944 10.18632/oncotarget.8064 26988913 PMC4991502 · DOI · Paper page
  86. [101]Wolf-Dennen K. Gordon N. Kleinerman E.S. Exosomal communication by metastatic osteosarcoma cells modulates alveolar macrophages to an M2 tumor-promoting phenotype and inhibits tumoricidal functions Oncoimmunology 2020 9 1747677 10.1080/2162402X.2020.1747677 32313728 PMC7153823 · DOI
  87. [102]Punzo F. Bellini G. Tortora C. Pinto D.D. Argenziano M. Pota E. Paola A.D. Martino M.D. Rossi F. Mifamurtide and TAM-like macrophages: Effect on proliferation, migration and differentiation of osteosarcoma cells Oncotarget 2020 11 687 698 10.18632/oncotarget.27479 32133045 PMC7041936 · DOI
  88. [103]Najafi M. Farhood B. Mortezaee K. Cancer stem cells (CSCs) in cancer progression and therapy J. Cell Physiol. 2019 234 8381 8395 10.1002/jcp.27740 30417375 · DOI
  89. [104]Posthuma DeBoer J. van Royen B.J. Helder M.N. Mechanisms of therapy resistance in osteosarcoma: A review Oncol. Discov. 2013 1 8 10.7243/2052-6199-1-8 · DOI
  90. [105]Honoki K. Fujii H. Kubo A. Kido A. Mori T. Tanaka Y. Tsujiuchi T. Possible involvement of stem-like populations with elevated ALDH1 in sarcomas for chemotherapeutic drug resistance Oncol. Rep. 2010 24 501 505 10.3892/or_00000885 20596639 · DOI
  91. [106]Tirino V. Desiderio V. Paino F. De Rosa A. Papaccio F. Fazioli F. Pirozzi G. Papaccio G. Human primary bone sarcomas contain CD133+ cancer stem cells displaying high tumorigenicity in vivo FASEB J. 2011 25 2022 2030 10.1096/fj.10-179036 21385990 · DOI
  92. [107]Adhikari A.S. Agarwal N. Wood B.M. Porretta C. Ruiz B. CD117 and Stro-1 identify osteosarcoma tumor-initiating cells associated with metastasis and drug resistance Cancer Res. 2010 70 4602 4612 10.1158/0008-5472.CAN-09-3463 20460510 PMC3139225 · DOI
  93. [108]Abarrategi A. Tornin J. Martinez-Cruzado L. Hamilton A. Martinez-Campos E. Rodrigo J.P. González M.V. Baldini N. Garcia-Castro J. Rodriguez R. Osteosarcoma: Cells-of-Origin, Cancer Stem Cells, and Targeted Therapies Stem Cells Int. 2016 2016 3631764 10.1155/2016/3631764 27366153 PMC4913005 · DOI
  94. [109]Cortini M. Massa A. Avnet S. Bonuccelli G. Baldini N. Tumor-Activated Mesenchymal Stromal Cells Promote Osteosarcoma Stemness and Migratory Potential via IL-6 Secretion PLoS ONE 2016 11 e0166500 10.1371/journal.pone.0166500 27851822 PMC5112800 · DOI
  95. [110]Brune J.C. Tormin A. Johansson M.C. Rissler P. Brosjö O. Löfvenberg R. von Steyern F.V. Mertens F. Rydholm A. Scheding S. Mesenchymal stromal cells from primary osteosarcoma are non-malignant and strikingly similar to their bone marrow counterparts Int. J. Cancer 2011 129 319 330 10.1002/ijc.25697 20878957 · DOI
  96. [111]Xiao W. Mohseny A.B. Hogendoorn P.C. Cleton-Jansen A.M. Mesenchymal stem cell transformation and sarcoma genesis Clin. Sarcoma Res. 2013 3 10 10.1186/2045-3329-3-10 23880362 PMC3724575 · DOI
  97. [112]Le Nail L.R. Brennan M. Rosset P. Deschaseaux F. Piloquet P. Pichon O. Le Caignec C. Crenn V. Layrolle P. Hérault O. Comparison of Tumor- and Bone Marrow-Derived Mesenchymal Stromal/Stem Cells from Patients with High-Grade Osteosarcoma Int. J. Mol. Sci. 2018 19 707 10.3390/ijms19030707 PMC5877568 29494553 · DOI
  98. [113]Ridge S.M. Sullivan F.J. Glynn S.A. Mesenchymal stem cells: Key players in cancer progression Mol. Cancer 2017 16 31 10.1186/s12943-017-0597-8 28148268 PMC5286812 · DOI
  99. [115]Bergfeld S.A. DeClerck Y.A. Bone marrow-derived mesenchymal stem cells and the tumor microenvironment Cancer Metastasis Rev. 2010 29 249 261 10.1007/s10555-010-9222-7 20411303 · DOI
  100. [116]Zhang P. Dong L. Yan K. Long H. Yang T.T. Dong M.Q. Zhou Y. Fan Q.Y. Ma B.A. CXCR4-mediated osteosarcoma growth and pulmonary metastasis is promoted by mesenchymal stem cells through VEGF Oncol. Rep. 2013 30 1753 1761 10.3892/or.2013.2619 23863999 · DOI · Paper page
  101. [117]Spaeth E.L. Dembinski J.L. Sasser A.K. Watson K. Klopp A. Hall B. Andreeff M. Marini F. Mesenchymal stem cell transition to tumor-associated fibroblasts contributes to fibrovascular network expansion and tumor progression PLoS ONE 2013 8 10.1371/annotation/4ab4c130-16cb-41f0-9507-b00ce070fbc6 PMC2661372 19352430 · DOI
  102. [119]Sainz B. Jr. Carron E. Vallespinós M. Machado H.L. Cancer Stem Cells and Macrophages: Implications in Tumor Biology and Therapeutic Strategies Mediat. Inflamm. 2016 2016 9012369 10.1155/2016/9012369 PMC4769767 26980947 · DOI
  103. [121]Yang L. Dong Y. Li Y. Wang D. Liu S. Wang D. Gao Q. Ji S. Chen X. Lei Q. IL-10 derived from M2 macrophage promotes cancer stemness via JAK1/STAT1/NF-κB/Notch1 pathway in non-small cell lung cancer Int. J. Cancer 2019 145 1099 1110 10.1002/ijc.32151 30671927 · DOI
  104. [122]Fan Q.M. Jing Y.Y. Yu G.F. Kou X.R. Ye F. Gao L. Li R. Zhao Q.D. Yang Y. Lu Z.H. Tumor-associated macrophages promote cancer stem cell-like properties via transforming growth factor-beta1-induced epithelial-mesenchymal transition in hepatocellular carcinoma Cancer Lett. 2014 352 160 168 10.1016/j.canlet.2014.05.008 24892648 · DOI
  105. [123]Mitchem J.B. Brennan D.J. Knolhoff B.L. Belt B.A. Zhu Y. Sanford D.E. Belaygorod L. Carpenter D. Collins L. Piwnica-Worms D. Targeting tumor-infiltrating macrophages decreases tumor-initiating cells, relieves immunosuppression, and improves chemotherapeutic responses Cancer Res. 2013 73 1128 1141 10.1158/0008-5472.CAN-12-2731 23221383 PMC3563931 · DOI
  106. [124]Asimakopoulos F. Kim J. Denu R.A. Hope C. Jensen J.L. Ollar S.J. Hebron E. Flanagan C. Callander N. Hematti P. Macrophages in multiple myeloma: Emerging concepts and therapeutic implications Leuk. Lymphoma 2013 54 2112 2121 10.3109/10428194.2013.778409 23432691 PMC3686978 · DOI
  107. [125]Chaturvedi P. Gilkes D.M. Takano N. Semenza G.L. Hypoxia-inducible factor-dependent signaling between triple-negative breast cancer cells and mesenchymal stem cells promotes macrophage recruitment Proc. Natl. Acad. Sci. USA 2014 111 E2120 E2129 10.1073/pnas.1406655111 24799675 PMC4034192 · DOI · Paper page
  108. [126]Perut F. Roncuzzi L. Baldini N. The Emerging Roles of Extracellular Vesicles in Osteosarcoma Front. Oncol. 2019 9 1342 10.3389/fonc.2019.01342 31850225 PMC6901498 · DOI
  109. [127]Raposo G. Stoorvogel W. Extracellular vesicles: Exosomes, microvesicles, and friends J. Cell. Biol. 2013 200 373 383 10.1083/jcb.201211138 23420871 PMC3575529 · DOI · Paper page
  110. [128]Garimella R. Washington L. Isaacson J. Vallejo J. Spence M. Tawfik O. Rowe P. Brotto M. Perez R. Extracellular Membrane Vesicles Derived from 143B Osteosarcoma Cells Contain Pro-Osteoclastogenic Cargo: A Novel Communication Mechanism in Osteosarcoma Bone Microenvironment Transl. Oncol. 2014 7 331 340 10.1016/j.tranon.2014.04.011 25180057 PMC4145399 · DOI
  111. [129]Troyer R.M. Ruby C.E. Goodall C.P. Yang L. Maier C.S. Albarqi H.A. Brady J.V. Bathke K. Taratula O. Mourich D. Exosomes from Osteosarcoma and normal osteoblast differ in proteomic cargo and immunomodulatory effects on T cells Exp. Cell. Res. 2017 358 369 376 10.1016/j.yexcr.2017.07.011 28712929 · DOI
  112. [130]Raimondi L. De Luca A. Gallo A. Costa V. Russelli G. Cuscino N. Manno M. Raccosta S. Carina V. Bellavia D. Osteosarcoma cell-derived exosomes affect tumor microenvironment by specific packaging of microRNAs Carcinogenesis 2019 bgz130 10.1093/carcin/bgz130 31294446 · DOI
  113. [131]Torreggiani E. Roncuzzi L. Perut F. Zini N. Baldini N. Multimodal transfer of MDR by exosomes in human osteosarcoma Int. J. Oncol. 2016 49 189 196 10.3892/ijo.2016.3509 27176642 · DOI
  114. [132]Yan B. Liu Q. Liu G. Huang X. Zhu G. Gao L. Xu Y. Macrophage-derived exosomes mediate osteosarcoma cell behavior by activating AKT signaling RSC Adv. 2020 10 5032 5039 10.1039/C9RA07332A PMC9049108 35498280 · DOI
  115. [133]Tu B. Peng Z.X. Fan Q.M. Du L. Yan W. Tang T.T. Osteosarcoma cells promote the production of pro-tumor cytokines in mesenchymal stem cells by inhibiting their osteogenic differentiation through the TGF-β/Smad2/3 pathway Exp. Cell. Res. 2014 320 164 173 10.1016/j.yexcr.2013.10.013 24183998 · DOI
  116. [134]Sousa S. Määttä J. The role of tumour-associated macrophages in bone metastasis J. Bone Oncol. 2016 5 135 138 10.1016/j.jbo.2016.03.004 27761375 PMC5063225 · DOI
  117. [135]Giurisato E. Lonardi S. Telfer B. Lussoso S. Risa-Ebri B. Zhang J. Russo I. Wang J. Santucci A. Finegan K. Extracellular-regulated protein kinase 5-mediated control of p21 expression promotes macrophage proliferation associated with tumor growth and metastasis Cancer Res. 2020 10.1158/0008-5472.CAN-19-2416 PMC7611207 32561530 · DOI
  118. [136]Bishop M.W. Janeway K.A. Gorlick R. Future directions in the treatment of osteosarcoma Curr. Opin. Pediatr. 2016 28 26 33 10.1097/MOP.0000000000000298 26626558 PMC4761449 · DOI
  119. [137]Heymann M.F. Brown H.K. Heymann D. Drugs in early clinical development for the treatment of osteosarcoma Expert Opin. Investig. Drugs 2016 25 1265 1280 10.1080/13543784.2016.1237503 27633385 · DOI
  120. [138]Liu B. Huang Y. Sun Y. Zhang J. Yao Y. Shen Z. Xiang D. He A. Prognostic value of inflammation-based scores in patients with osteosarcoma Sci. Rep. 2016 6 39862 10.1038/srep39862 28008988 PMC5180218 · DOI
  121. [139]Endo-Munoz L. Evdokiou A. Saunders N.A. The role of osteoclasts and tumour-associated macrophages in osteosarcoma metastasis Biochim. Biophys. Acta 2012 1826 434 442 10.1016/j.bbcan.2012.07.003 22846337 · DOI
  122. [140]Meyers P.A. Schwartz C.L. Krailo M. Kleinerman E.S. Betcher D. Bernstein M.L. Conrad E. Ferguson W. Gebhardt M. Goorin A.M. Osteosarcoma: A randomized, prospective trial of the addition of ifosfamide and/or muramyl tripeptide to cisplatin, doxorubicin, and high-dose methotrexate J. Clin. Oncol. 2005 23 2004 2011 10.1200/JCO.2005.06.031 15774791 · DOI
  123. [143]Kleinerman E.S. Raymond A.K. Bucana C.D. Jaffe N. Harris M.B. Krakoff I.H. Benjamin R. Fidler I.J. Unique histological changes in lung metastases of osteosarcoma patients following therapy with liposomal muramyl tripeptide (CGP 19835A lipid) Cancer Immunol. Immunother. 1992 34 211 220 10.1007/BF01741788 1537053 PMC11038889 · DOI
  124. [144]Kleinerman E.S. Gano J.B. Johnston D.A. Benjamin R.S. Jaffe N. Efficacy of liposomal muramyl tripeptide (CGP 19835A) in the treatment of relapsed osteosarcoma Am. J. Clin. Oncol. 1995 18 93 99 10.1097/00000421-199504000-00001 7900714 · DOI
  125. [145]Pahl J.H. Kwappenberg K.M. Varypataki E.M. Santos S.J. Kuijjer M.L. Mohamed S. Wijnen J.T. van Tol M.J. Cleton-Jansen A.M. Egeler R.M. Macrophages inhibit human osteosarcoma cell growth after activation with the bacterial cell wall derivative liposomal muramyl tripeptide in combination with interferon-γ J. Exp. Clin. Cancer Res. 2014 33 27 10.1186/1756-9966-33-27 24612598 PMC4007518 · DOI
  126. [146]Ando K. Mori K. Corradini N. Redini F. Heymann D. Mifamurtide for the treatment of nonmetastatic osteosarcoma Expert. Opin. Pharmacother. 2011 12 285 292 10.1517/14656566.2011.543129 21226638 PMC3413631 · DOI
  127. [147]Li X. Chen Y. Liu X. Zhang J. He X. Teng G. Yu D. Tim3/Gal9 interactions between T cells and monocytes result in an immunosuppressive feedback loop that inhibits Th1 responses in osteosarcoma patients Int. Immunopharmacol. 2017 44 153 159 10.1016/j.intimp.2017.01.006 28103502 · DOI
  128. [148]Oldridge E.E. Walker H.F. Stower M.J. Simms M.S. Mann V.M. Collins A.T. Pellacani D. Maitland N.J. Retinoic acid represses invasion and stem cell phenotype by induction of the metastasis suppressors RARRES1 and LXN Oncogenesis 2013 2 e45 10.1038/oncsis.2013.6 23588494 PMC3641360 · DOI
  129. [149]Cheng J. Qi J. Li X.T. Zhou K. Xu J.H. Zhou Y. Zhang G.Q. Xu J.P. Zhou R.J. ATRA and Genistein synergistically inhibit the metastatic potential of human lung adenocarcinoma cells Int. J. Clin. Exp. Med. 2015 8 4220 4227 26064333 PMC4443167
  130. [150]Kimura Y. Sumiyoshi M. Antitumor and antimetastatic actions of dihydroxycoumarins (esculetin or fraxetin) through the inhibition of M2 macrophage differentiation in tumor-associated macrophages and/or G1 arrest in tumor cells Eur. J. Pharmacol. 2015 746 115 125 10.1016/j.ejphar.2014.10.048 25445053 · DOI
  131. [151]Tsagozis P. Eriksson F. Pisa P. Zoledronic acid modulates antitumoral responses of prostate cancer-tumor associated macrophages Cancer Immunol. Immunother. 2008 57 1451 1459 10.1007/s00262-008-0482-9 18297280 PMC11030129 · DOI
  132. [152]Junankar S. Shay G. Jurczyluk J. Ali N. Down J. Pocock N. Parker A. Nguyen A. Sun S. Kashemirov B. Real-time intravital imaging establishes tumor-associated macrophages as the extraskeletal target of bisphosphonate action in cancer Cancer Discov. 2015 5 35 42 10.1158/2159-8290.CD-14-0621 25312016 PMC4293349 · DOI
  133. [153]Dass C.R. Choong P.F. Zoledronic acid inhibits osteosarcoma growth in an orthotopic model Mol. Cancer Ther. 2007 6 3263 3270 10.1158/1535-7163.MCT-07-0546 18089720 · DOI
  134. [154]Labrinidis A. Hay S. Liapis V. Ponomarev V. Findlay D.M. Evdokiou A. Zoledronic acid inhibits both the osteolytic and osteoblastic components of osteosarcoma lesions in a mouse model Clin. Cancer Res. 2009 15 3451 3461 10.1158/1078-0432.CCR-08-1616 19401351 PMC5568249 · DOI
  135. [155]Ory B. Heymann M.F. Kamijo A. Gouin F. Heymann D. Redini F. Zoledronic acid suppresses lung metastases and prolongs overall survival of osteosarcoma-bearing mice Cancer 2005 104 2522 2529 10.1002/cncr.21530 16270320 · DOI · Paper page
  136. [156]Van Rooijen N. Sanders A. Elimination, blocking, and activation of macrophages: Three of a kind? J. Leukoc. Biol. 1997 62 702 709 10.1002/jlb.62.6.702 9400810 · DOI
  137. [157]Chen Q. Zhang X.H. Massagué J. Macrophage binding to receptor VCAM-1 transmits survival signals in breast cancer cells that invade the lungs Cancer Cell 2011 20 538 549 10.1016/j.ccr.2011.08.025 22014578 PMC3293160 · DOI · Paper page
  138. [158]Dhupkar P. Gordon N. Stewart J. Kleinerman E.S. Anti-PD-1 therapy redirects macrophages from an M2 to an M1 phenotype inducing regression of OS lung metastases Cancer Med. 2018 7 2654 2664 10.1002/cam4.1518 29733528 PMC6010882 · DOI
  139. [159]Pinto N. Park J.R. Murphy E. Yearley J. McClanahan T. Annamalai L. Hawkins D.S. Rudzinski E.R. Patterns of PD-1, PD-L1, and PD-L2 expression in pediatric solid tumors Pediatr. Blood Cancer 2017 64 10.1002/pbc.26613 28488345 · DOI
  140. [160]Shen J.K. Cote G.M. Choy E. Yang P. Harmon D. Schwab J. Nielsen G.P. Chebib I. Ferrone S. Wang X. Programmed cell death ligand 1 expression in osteosarcoma Cancer Immunol. Res. 2014 2 690 698 10.1158/2326-6066.CIR-13-0224 24866169 PMC4082476 · DOI
  141. [161]Sundara Y.T. Kostine M. Cleven A.H. Bovée J.V. Schilham M.W. Cleton-Jansen A.M. Increased PD-L1 and T-cell infiltration in the presence of HLA class I expression in metastatic high-grade osteosarcoma: A rationale for T-cell-based immunotherapy Cancer Immunol. Immunother. 2017 66 119 128 10.1007/s00262-016-1925-3 27853827 PMC5222929 · DOI · Paper page
  142. [162]Van Erp A.E.M. Versleijen-Jonkers Y.M.H. Hillebrandt-Roeffen M.H.S. van Houdt L. Gorris M.A.J. van Dam L.S. Mentzel T. Weidema M.E. Savci-Heijink C.D. Desar I.M.E. Expression and clinical association of programmed cell death-1, programmed death-ligand-1 and CD8+ lymphocytes in primary sarcomas is subtype dependent Oncotarget 2017 8 71371 71384 10.18632/oncotarget.19071 29050367 PMC5642642 · DOI
  143. [163]Zhu Z. Jin Z. Zhang M. Tang Y. Yang G. Yuan X. Yao J. Sun D. Prognostic value of programmed death-ligand 1 in sarcoma: A meta-analysis Oncotarget 2017 8 59570 59580 10.18632/oncotarget.19168 28938660 PMC5601756 · DOI
  144. [164]Lussier D.M. O’Neill L. Nieves L.M. McAfee M.S. Holechek S.A. Collins A.W. Dickman P. Jacobsen P.J. Hingorani P. Blattman J.N. Enhanced T-cell immunity to osteosarcoma through antibody blockade of PD-1/PD-L1 interactions J. Immunother. 2015 38 96 106 10.1097/CJI.0000000000000065 25751499 PMC6426450 · DOI · Paper page
  145. [165]Wang L. Zhang Q. Chen W. Shan B. Ding Y. Zhang G. Cao N. Liu L. Zhang Y. B7-H3 is overexpressed in patients suffering osteosarcoma and associated with tumor aggressiveness and metastasis PLoS ONE 2013 8 e70689 10.1371/journal.pone.0070689 23940627 PMC3734259 · DOI
  146. [166]Kaneda M.M. Messer K.S. Ralainirina N. Li H. Leem C.J. Gorjestani S. Woo G. Nguyen A.V. Figueiredo C.C. Foubert P. PI3Kγ is a molecular switch that controls immune suppression Nature 2016 539 437 442 10.1038/nature19834 27642729 PMC5479689 · DOI
  147. [167]Liu M. Tong Z. Ding C. Luo F. Wu S. Wu C. Albeituni S. He L. Hu X. Tieri D. Transcription factor c-Maf is a checkpoint that programs macrophages in lung cancer J. Clin. Investig. 2020 130 2081 2096 10.1172/JCI131335 31945018 PMC7108920 · DOI
  148. [168]Zanganeh S. Hutter G. Spitler R. Lenkov O. Mahmoudi M. Shaw A. Pajarinen J.S. Nejadnik H. Goodman S. Moseley M. Iron oxide nanoparticles inhibit tumour growth by inducing pro-inflammatory macrophage polarization in tumour tissues Nat. Nanotechnol. 2016 11 986 994 10.1038/nnano.2016.168 27668795 PMC5198777 · DOI · Paper page
  149. [169]Boraschi D. Italiani P. Palomba R. Decuzzi P. Duschl A. Fadeel B. Moghimi S.M. Nanoparticles and innate immunity: New perspectives on host defence Semin. Immunol. 2017 34 33 51 10.1016/j.smim.2017.08.013 28869063 · DOI
  150. [170]Li K. Lu L. Xue C. Liu J. He Y. Zhou J. Xia Z. Dai L. Luo Z. Mao Y. Polarization of tumor-associated macrophage phenotype via porous hollow iron nanoparticles for tumor immunotherapy in vivo Nanoscale 2020 12 130 144 10.1039/C9NR06505A 31799577 · DOI
  151. [171]Gomez-Brouchet A. Illac C. Gilhodes J. Bouvier C. Aubert S. Guinebretiere J.M. Marie B. Larousserie F. Entz-Werle N. de Pinieux G. CD163-positive tumor-associated macrophages and CD8-positive cytotoxic lymphocytes are powerful diagnostic markers for the therapeutic stratification of osteosarcoma patients: An immunohistochemical analysis of the biopsies fromthe French OS2006 phase 3 trial Oncoimmunology 2017 6 e1331193 28932633 PMC5599091
  152. [172]Fritzsching B. Fellenberg J. Moskovszky L. Sapi Z. Krenacs T. Machado I. Poeschl J. Lehner B. Szendroi M. Bosch A.L. CD8(+)/FOXP3(+)-ratio in osteosarcoma microenvironment separates survivors from non-survivors: A multicenter validated retrospective study Oncoimmunology 2015 4 e990800 10.4161/2162402X.2014.990800 25949908 PMC4404826 · DOI
  153. [173]Klichinsky M. Ruella M. Shestova O. Lu X.M. Best A. Zeeman M. Schmierer M. Gabrusiewicz K. Anderson N.R. Petty N.E. Human chimeric antigen receptor macrophages for cancer immunotherapy Nat Biotechnol. 2020 10.1038/s41587-020-0462-y PMC7883632 32361713 · DOI · Paper page

Cited by

Sorted by citations

Authors
Cersosimo, F., Lonardi, S., Bernardini, G., Telfer, B., Mandelli, G. E., Santucci, A., Vermi, W., & Giurisato, E.
Affiliations
  • University of Siena (IT)
  • University of Brescia (IT)
  • University of Manchester (GB)
  • Washington University in St. Louis (US)
Corresponding author
Giurisato, Emanuele
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2020-07-23
Volume
21
Issue
15
Pages
5207
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms21155207
PMC
PMC7432207
OpenAlex
W3045264243
Cited by
280
References
20
Citations by year
2026: 38 · 2025: 65 · 2024: 50 · 2023: 46 · 2022: 45 · 2021: 30 · 2020: 6
FWCI
3.10
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion)
  • Use Siena air (University of Siena) (submittedVersion, cc-by)
Funders
  • Università degli Studi di Siena (PSR2020)
  • Fondazione Beretta
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Keywords
osteosarcoma, tumor-associated macrophages, M2 macrophages, tumor microenvironment, metastasis, cancer stem cells, targeted therapy, prognosis
MeSH terms
Tumor-Associated Macrophages, Bone Neoplasms, Humans, Neoplasm Metastasis, Osteosarcoma, Signal Transduction, Tumor Microenvironment

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