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Tumor Microenvironment: Comparison Between Primary Origin Tumors and Corresponding Brain Metastasis

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Principles of Neuro-Oncology

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Abstract

The present review aims to discuss the contemporary medical literature involving the variances between the tumor microenvironment (TME) mainly in melanoma, lung, and breast cancer in their original primary site and compare them with their brain metastases (BM). The TME plays a fundamental role in the behavior of cancer. In the process of carcinogenesis, cells such as fibroblasts, macrophages, endothelial cells, NK cells, etc., through the secretion of molecules can perpetuate and progress carcinogenesis. The conditions at the TME, such as oxygen concentration, growth factors, and receptors, generate the beginning of angiogenesis; this is an example of the importance of microenvironmental conditions in the performance of neoplastic cells. The most frequent malignant tumors of the brain are metastatic in origin, mainly from lung, breast, and melanoma. Metastatic cancer cells have to adhere to and penetrate the blood brain barrier (BBB); after passing through the BBB they have to survive by producing a variety of cytokines, chemokines and mediators to modify their new TME. A field currently studied is the microenvironment of these metastases, since this has brought about the discovery of new therapeutic targets. In these three types of tumors, treatment is more effective in the primary tumor than in the BM, due to many factors including the blood brain barrier. Understanding the differences in the characteristics of the microenvironment surrounding the primary tumor and their respective metastasis might improve strategies to grasp cancer behavior. This chapter will focus on the relationship between the tumor microenvironment of primary origin tumor and their corresponding brain metastases.

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References

  1. Chitty JL, Filipe EC, Lucas MC, Herrmann D, Cox TR, Timpson P. Recent advances in understanding the complexities of metastasis. F1000Research. 2018 Aug;7:1169.

    Article  CAS  Google Scholar 

  2. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011 Mar;144(5):646–74.

    Article  CAS  PubMed  Google Scholar 

  3. Pietilä M, Ivaska J, Mani SA. Whom to blame for metastasis, the epithelial–mesenchymal transition or the tumor microenvironment? Cancer Lett. 2016;380(1):359–68.

    Article  PubMed  Google Scholar 

  4. Ebben JD, You M. Brain metastasis in lung cancer: building a molecular and systems-level understanding to improve outcomes. Int J Biochem Cell Biol. 2016 Sep;78:288–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Wei SC, Duffy CR, Allison JP. Fundamental mechanisms of immune checkpoint blockade therapy. Cancer Discov. 2018 Sep;8(9):1069–86.

    Article  PubMed  Google Scholar 

  6. Pearce OMT, Delaine-Smith RM, Maniati E, Nichols S, Wang J, Böhm S, et al. Deconstruction of a metastatic tumor microenvironment reveals a common matrix response in human cancers. Cancer Discov. 2018 Mar 1;8(3):304–19.

    Article  CAS  PubMed  Google Scholar 

  7. Arrieta VA, Cacho-Díaz B, Zhao J, Rabadan R, Chen L, Sonabend AM. The possibility of cancer immune editing in gliomas: a critical review. OncoImmunology. 2018 May;7(7):1–9.

    Article  Google Scholar 

  8. Mani SA, Guo W, Liao M-J, Eaton EN, Ayyanan A, Zhou AY, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008 May;133(4):704–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Yang J, Mani SA, Donaher JL, Ramaswamy S, Itzykson RA, Come C, et al. Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell. 2004 Jun;117(7):927–39.

    Article  CAS  PubMed  Google Scholar 

  10. Wong GS, Rustgi AK. Matricellular proteins: priming the tumour microenvironment for cancer development and metastasis. Br J Cancer. 2013 Jan 15;108:755–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Wu K, Sharma S, Venkat S, Liu K, Zhou X, Watabe K. Non-coding RNAs in cancer brain metastasis. Front Biosci (Schol Ed). 2016 Jan;8:187–202.

    Article  Google Scholar 

  12. Sleeboom JJF, Eslami Amirabadi H, Nair P, Sahlgren CM, den Toonder JMJ. Metastasis in context: modeling the tumor microenvironment with cancer-on-a-chip approaches. Dis Models Amp Mech. 2018 Mar 1;11(3):dmm033100.

    Article  Google Scholar 

  13. Singh R, Mo Y-Y. Role of microRNAs in breast cancer. Cancer Biol Ther. 2014 Oct;14(3):201–12.

    Article  Google Scholar 

  14. McGuire A, Brown JAL, Kerin MJ. Metastatic breast cancer: the potential of miRNA for diagnosis and treatment monitoring. Cancer Metastasis Rev. 2015 Feb;34(1):145–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Yao D, Dai C, Peng S. Mechanism of the mesenchymal-epithelial transition and its relationship with metastatic tumor formation. Mol Cancer Res. 2011 Dec;9(12):1608–20.

    Article  CAS  PubMed  Google Scholar 

  16. Chao Y, Wu Q, Acquafondata M, Dhir R, Wells A. Partial Mesenchymal to epithelial reverting transition in breast and prostate cancer metastases. Cancer Microenviron. 2011 Sep;5(1):19–28.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Ursini-Siegel J, Siegel PM. The influence of the pre-metastatic niche on breast cancer metastasis. Cancer Lett. 2015 Nov;380:1–8.

    Google Scholar 

  18. Said NABM, Williams ED. Growth factors in induction of epithelial-mesenchymal transition and metastasis. Cells Tissues Organs. 2011;193(1–2):85–97.

    Article  CAS  PubMed  Google Scholar 

  19. Mittal V. Epithelial mesenchymal transition in tumor metastasis. Annu Rev Pathol Mech Dis. 2018 Jan;13(1):395–412.

    Article  CAS  Google Scholar 

  20. Chang YS, di Tomaso E, McDonald DM, Jones R, Jain RK, Munn LL. Mosaic blood vessels in tumors: frequency of cancer cells in contact with flowing blood. Proc Natl Acad Sci U S A. 2000 Dec;97(26):14608–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Pantel K, Speicher MR. The biology of circulating tumor cells. Oncogene. 2015 Jun;35(10):1216–24.

    Article  PubMed  Google Scholar 

  22. Kanikarla-Marie P, Lam M, Menter DG, Kopetz S. Platelets, circulating tumor cells, and the circulome. Cancer Metastasis Rev. 2017 Aug;36:1–14.

    Article  Google Scholar 

  23. Nilsson RJA, Balaj L, Hulleman E, van Rijn S, Pegtel DM, Walraven M, et al. Blood platelets contain tumor-derived RNA biomarkers. Blood. 2011 Sep 29;118(13):3680–3.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Wrobel JK, Toborek M. Blood–brain barrier remodeling during brain metastasis formation. Mol Med. 2016;22(1):1.

    Article  Google Scholar 

  25. Daneman R, Prat A. The blood–brain barrier. Cold Spring Harb Perspect Biol. 2015 Jan;7(1):a020412.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Stamatovic SM, Keep RF, Andjelkovic AV. Brain endothelial cell-cell junctions: how to “open” the blood brain barrier. Curr Neuropharmacol. 2008 Sep;6(3):179–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Wolburg H, Lippoldt A. Tight junctions of the blood-brain barrier: development, composition and regulation. Vascul Pharmacol. 2002 Jun;38(6):323–37.

    Article  CAS  PubMed  Google Scholar 

  28. Butt AM, Jones HC, Abbott NJ. Electrical resistance across the blood-brain barrier in anaesthetized rats: a developmental study. J Physiol. 1990 Oct;429:47–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Feng S, Cen J, Huang Y, Shen H, Yao L, Wang Y, et al. Matrix Metalloproteinase-2 and -9 secreted by leukemic cells increase the permeability of blood-brain barrier by disrupting tight junction proteins. PLoS One. 2011 Aug;6(8):e20599.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Bos PD, Zhang XHF, Nadal C, Shu W, Gomis RR, Nguyen DX, et al. Genes that mediate breast cancer metastasis to the brain. Nature. 2009 Jun;459(7249):1005–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Boecke A, Carstens AC, Neacsu CD, Baschuk N, Haubert D, Kashkar H, et al. TNF-receptor-1 adaptor protein FANmediates TNF-induced B16 melanomamotility and invasion. Br J Cancer. 2013 May:1–11.

    Google Scholar 

  32. Lucas JT, Salimath BP, Slomiany MG, Rosenzweig SA. Regulation of invasive behavior by vascular endothelial growth factor is HEF1-dependent. Oncogene. 2010 May;29(31):4449–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Rasmussen MK, Mestre H, Nedergaard M. Rapid review. Lancet Neurol. 2018 Oct;17(11):1016–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Paku S, Döme B, Tóth R, Timár J. Organ-specificity of the extravasation process: an ultrastructural study. Clin Exp Metastasis. 2000 Oct;18(6):481–92.

    Article  CAS  PubMed  Google Scholar 

  35. Winkler F. The brain metastatic niche. J Mol Med. 2015 Oct;93(11):1213–20.

    Article  CAS  PubMed  Google Scholar 

  36. Reymond N, d’Água BB, Ridley AJ. Crossing the endothelial barrier during metastasis. Nat Rev Cancer. 2013 Dec;13(12):858–70.

    Article  CAS  PubMed  Google Scholar 

  37. Avraham HK, Jiang S, Fu Y, Nakshatri H, Ovadia H, Avraham S. Angiopoietin-2 mediates blood-brain barrier impairment and colonization of triple-negative breast cancer cells in brain. J Pathol. 2014 Jan;232(3):369–81.

    Article  CAS  PubMed  Google Scholar 

  38. Jacus MO, Daryani VM, Harstead KE, Patel YT, Throm SL, Stewart CF. Pharmacokinetic properties of anticancer Agentsfor the treatment of central nervous system tumors: update of the literature. Clin Pharmacokinet. 2015 Aug:1–15.

    Google Scholar 

  39. Cacho-Díaz B. Factors associated with long-term survival in central nervous system metastases. J Neurooncol. 2018 Jul;140:159–64.

    Article  PubMed  Google Scholar 

  40. Quail DF, Joyce JA. Microenvironmental regulation of tumor progression and metastasis. Nat Med. 2013 Nov;19(11):1423–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Lowery FJ, Yu D. Brain metastasis: unique challenges and open opportunities. Biochim Biophys Acta BBA – Rev Cancer. 2017;1867(1):49–57.

    Article  CAS  Google Scholar 

  42. Rolland Y, Demeule M, Fenart L, Béliveau R. Inhibition of melanoma brain metastasis by targeting melanotransferrin at the cell surface. Pigment Cell Melanoma Res. 2009 Feb;22(1):86–98.

    Article  CAS  PubMed  Google Scholar 

  43. Li B, Zhao W-D, Tan Z-M, Fang W-G, Zhu L, Chen Y-H. Involvement of rho/ROCK signalling in small cell lung cancer migration through human brain microvascular endothelial cells. FEBS Lett. 2006 Jun;580(17):4252–60.

    Article  CAS  PubMed  Google Scholar 

  44. Lee B-C, Lee TH, Avraham S, Avraham HK. Involvement of the chemokine receptor CXCR4 and its ligand stromal cell-derived factor 1alpha in breast cancer cell migration through human brain microvascular endothelial cells. Mol Cancer Res MCR. 2004 Jun;2(6):327–38.

    Article  CAS  PubMed  Google Scholar 

  45. Tominaga N, Kosaka N, Ono M, Katsuda T, Yoshioka Y, Tamura K, et al. Brain metastatic cancer cells release microRNA-181c-containing extracellular vesicles capable ofdestructing blood–brain barrier. Nat Commun. 2015 Mar;6:1–12.

    Article  Google Scholar 

  46. Zhang RD, Price JE, Fujimaki T, Bucana CD, Fidler IJ. Differential permeability of the blood-brain barrier in experimental brain metastases produced by human neoplasms implanted into nude mice. Am J Pathol. 1992 Nov;141(5):1115–24.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. de Vries HE, Blom-Roosemalen MC, van Oosten M, de Boer AG, van Berkel TJ, Breimer DD, et al. The influence of cytokines on the integrity of the blood-brain barrier in vitro. J Neuroimmunol. 1996 Jan;64(1):37–43.

    Article  PubMed  Google Scholar 

  48. Kang S-A, Hasan N, Mann AP, Zheng W, Zhao L, Morris L, et al. Blocking the adhesion cascade at the premetastatic niche for prevention of breast Cancer metastasis. Mol Ther. 2015 Jun;23(6):1044–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Weidle UH, Birzele F, Kollmorgen G, Rüger R. Dissection of the process of brain metastasis reveals targets and mechanisms for molecular-based intervention. Cancer Genomics Proteomics. 2016 Jul;13(4):245–58.

    CAS  PubMed  Google Scholar 

  50. Fong MY, Zhou W, Liu L, Alontaga AY, Chandra M, Ashby J, et al. Breast-cancer-secreted miR-122 reprograms glucose metabolism in premetastatic niche to promote metastasis. Nat Cell Biol. 2015 Jan;17(2):183–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Fidler IJ. The biology of brain metastasis: challenges for therapy. Cancer J Sudbury Mass. 2018 Oct;21(4):284–93.

    Article  Google Scholar 

  52. Valiente M, Ahluwalia MS, Boire A, Brastianos PK, Goldberg SB, Lee EQ, et al. The evolving landscape of brain metastasis. Trends Cancer. 2018 Mar;4(3):176–96.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Valiente M, Obenauf AC, Jin X, Chen Q, Zhang XHF, Lee DJ, et al. Serpins promote cancer cell survival and vascular co-option in brain metastasis. Cell. 2014 Feb;156(5):1002–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Kim S-J, Kim J-S, Park ES, Lee J-S, Lin Q, Langley RR, et al. Astrocytes upregulate survival genes in tumor cells and induce protection from chemotherapy. Neoplasia. 2011 Mar;13(3):286–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Quail DF, Joyce JA. The microenvironmental landscape of brain tumors. Cancer Cell. 2017 Mar;31(3):326–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Wood SL, Pernemalm M, Crosbie PA, Whetton AD. The role of the tumor-microenvironment in lung cancer-metastasis and its relationship to potential therapeutic targets. Cancer Treat Rev. 2014 May 1;40(4):558–66.

    Article  CAS  PubMed  Google Scholar 

  57. Lorger M, Felding-Habermann B. Capturing changes in the brain microenvironment during initial steps of breast cancer brain metastasis. Am J Pathol. 2010 Jun;176(6):2958–71.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Tamagno I, Schiffer D. Nestin expression in reactive astrocytes of human pathology. J Neurooncol. 2006 Jul;80(3):227–33.

    Article  CAS  PubMed  Google Scholar 

  59. Termini J, Neman J, Jandial R. Role of the neural niche in brain metastatic cancer. Cancer Res. 2014 Jul;74(15):4011–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Kienast Y, von Baumgarten L, Fuhrmann M, Klinkert WEF, Goldbrunner R, Herms J, et al. Real-time imaging reveals the single steps of brain metastasis formation. Nat Med. 2009 Dec 20;16:116.

    Article  PubMed  Google Scholar 

  61. Holmgren L, O’Reilly MS, Folkman J. Dormancy of micrometastases: balanced proliferation and apoptosis in the presence of angiogenesis suppression. Nat Med. 1995 Feb;1(2):149–53.

    Article  CAS  PubMed  Google Scholar 

  62. Hoshide R. The role of the neural niche in brain metastasis. Clin Exp Metastasis. 2017 Sep;34:369–76.

    Article  PubMed  Google Scholar 

  63. Dagogo-Jack I, Carter SL, Brastianos PK. Brain metastasis: clinical implications of branched evolution. Trends Cancer. 2016 Jul 1;2(7):332–7.

    Article  PubMed  Google Scholar 

  64. Huchzermeyer C, Berndt N, Holzhütter H-G, Kann O. Oxygen consumption rates during three different neuronal activity states in the hippocampal CA3 network. J Cereb Blood Flow Amp Metab. 2012 Nov;33(2):263–71.

    Article  Google Scholar 

  65. Witzel I, Oliveira-Ferrer L, Pantel K, Müller V, Wikman H. Breast cancer brain metastases: biology and new clinical perspectives. Breast Cancer Res. 2016 Jan;18(1):1–9.

    Article  Google Scholar 

  66. Cacho-Diaz B, Spinola-Marono H, Arrieta VA, Granados-Garcia M, Wegman-Ostrosky T, Mendoza-Olivas LG, et al. Diagnosis of brain metastases in breast cancer patients resulting from neurological symptoms. Clin Neurol Neurosurg. 2018 Oct;173:61–4.

    Article  PubMed  Google Scholar 

  67. Jeevan DS, Cooper JB, Braun A, Murali R, Jhanwar-Uniyal M. Molecular pathways mediating metastases to the brain via epithelial-to-mesenchymal transition: genes, proteins, and functional analysis. Anticancer Res. 2016 Feb;36(2):523–32.

    CAS  PubMed  Google Scholar 

  68. Shen L, Chen L, Wang Y, Jiang X, Xia H, Zhuang Z. Long noncoding RNA MALAT1 promotes brain metastasis by inducing epithelial-mesenchymal transition in lung cancer. J Neurooncol. 2014 Sep;121(1):101–8.

    Article  PubMed  Google Scholar 

  69. Schnepp PM, Lee DD, Guldner IH, O’Tighearnaigh TK, Howe EN, Palakurthi B, et al. GAD1 Upregulation programs aggressive features of Cancer cell metabolism in the brain metastatic microenvironment. Cancer Res. 2017 May;77(11):2844–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Choy C, Ansari KI, Neman J, Hsu S, Duenas MJ, Li H, et al. Cooperation of neurotrophin receptor TrkBand Her2 in breast cancer cells facilitatesbrain metastases. Breast Cancer Res. 2017 Apr;19(1):1–11.

    Article  Google Scholar 

  71. Ferguson SD, Zheng S, Xiu J, Zhou S, Khasraw M, Brastianos PK, et al. Profiles of brain metastases: prioritization of therapeutic targets. Int J Cancer. 2018 Oct;143(11):3019–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Stark MS, Klein K, Weide B, Haydu LE, Pflugfelder A, Tang YH, et al. The prognostic and predictive value of melanoma-related MicroRNAs using tissue and serum: a MicroRNA expression analysis. EBioMedicine. 2015 Jul;2(7):671–80.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Castro D, Moreira M, Gouveia AM, Pozza DH, De Mello RA. MicroRNAs in lung cancer. Oncotarget. 2017 Oct;8(46):81679–85.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Zhao M, Wang S, Li Q, Ji Q, Guo P, Liu X. MALAT1: a long non-coding RNA highly associated with human cancers (review). Oncol Lett. 2018 May;16(1):19–26.

    PubMed  PubMed Central  Google Scholar 

  75. Barciszewska A-M. Global DNA demethylation as an epigenetic marker of human brain metastases. Biosci Rep. 2018 Oct;38(5):BSR20180731.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Woditschka S, Evans L, Duchnowska R, Reed LT, Palmieri D, Qian Y, et al. DNA double-strand break repair genes and oxidative damage in brain metastasis of breast cancer. JNCI J Natl Cancer Inst. 2014 Jun;106(7):352.

    Article  Google Scholar 

  77. Lanman TA, Kesari S, Patel SP, Bazhenova L, Parker BA, Daniels GA, et al. Comparison of tissue DNA to circulating tumor DNA in patients with brain metastases. J Clin Oncol. 2017 May 20;35(15 suppl):e13546.

    Article  Google Scholar 

  78. Aljohani HM, Aittaleb M, Furgason JM, Amaya P, Deeb A, Chalmers JJ, et al. Genetic mutations associated with lung cancer metastasis to the brain. Mutagenesis. 2018 Apr;33(2):137–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Hannan EJ, O’Leary DP, MacNally SP, Kay EW, Farrell MA, Morris PG, et al. The significance of BRAF V600E mutation status discordance between primary cutaneous melanoma and brain metastases. Medicine (Baltimore). 2017 Dec;96(48):e8404.

    Article  CAS  Google Scholar 

  80. El-Telbany A, Ma PC. Cancer genes in lung cancer: racial disparities: are there any? Genes Cancer. 2012 Dec;3(7–8):467–80.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Kim H, Xu X, Yoo S-B, Sun P-L, Jin Y, Paik JH, et al. Discordance between anaplastic lymphoma kinase status in primary non-small-cell lung cancers and their corresponding metastases. Histopathology. 2012 Sep;62(2):305–14.

    Article  CAS  PubMed  Google Scholar 

  82. Han CH, Brastianos PK. Genetic characterization of brain metastases in the era of targeted therapy. Front Oncol. 2017;7:230.

    Article  PubMed  PubMed Central  Google Scholar 

  83. Berghoff AS. Tumor infiltrating lymphocytes and PD-L1 expression in brain metastases of small cell lung cancer (SCLC). 2016 Oct;130(1):19–29.

    Google Scholar 

  84. Ogiya R, Niikura N, Kumaki N, Yasojima H, Iwasa T, Kanbayashi C, et al. Comparison of immune microenvironments between primary tumors and brain metastases in patients with breast cancer. Oncotarget. 2017 Nov 28;8(61):103671–81.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Qian B-Z, Pollard JW. Macrophage diversity enhances tumor progression and metastasis. Cell. 2010 Apr;141(1):39–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Sugihara AQ, Rolle CE, Lesniak MS. Regulatory T cells actively infiltrate metastatic brain tumors. Int J Oncol. 2009 May;34(6):1533–40.

    PubMed  Google Scholar 

  87. Mansfield AS, Aubry MC, Moser JC, Harrington SM, Dronca RS, Park SS, et al. Temporal and spatial discordance of programmed cell death-ligand 1 expression and lymphocyte tumor infiltration between paired primary lesions and brain metastases in lung cancer. Ann Oncol. 2016 Sep;27(10):1953–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Duchnowska R, Pęksa R, Radecka B, Mandat T, Trojanowski T, Jarosz B, et al. Immune response in breast cancer brain metastases and their microenvironment: the role of the PD-1/PD-L axis. Breast Cancer Res. 2016 Apr:1–11.

    Google Scholar 

  89. Cacho-Díaz B, García-Botello DR, Wegman-Ostrosky T, Reyes-Soto G, Ortiz-Sánchez E, Herrera-Montalvo LA. Tumor microenvironment differences between primary tumor and brain metastases. J Transl Med. 2020;18. https://doi.org/10.1186/s12967-019-02189-8.

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Authors and Affiliations

  1. Neuro-oncology Unit, Instituto Nacional de Cancerología, Mexico City, Mexico

    Bernardo Cacho-Díaz & Donovan R. García-Botello

  2. Research Unit, Instituto Nacional de Cancerología, Mexico City, Mexico

    Talia Wegman-Ostrosky, Elizabeth Ortiz-Sánchez & Luis Alonso Herrera-Montalvo

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  1. Bernardo Cacho-Díaz
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  2. Donovan R. García-Botello
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Editors and Affiliations

  1. Department of Neurosurgery, Aurora Neuroscience Innovation Institute, Milwaukee, WI, USA

    Alejandro Monroy-Sosa

  2. Department of Neurosurgery, Aurora Neuroscience Innovation Institute, Milwaukee, WI, USA

    Srikant S. Chakravarthi

  3. Instituto Nacional de Cancerología, Mexico City, Mexico

    Jaime G. de la Garza-Salazar

  4. Instituto Nacional de Cancerología, Mexico City, Mexico

    Abelardo Meneses Garcia

  5. Neeka Health, LLC, Milwaukee, WI, USA

    Amin B. Kassam

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Cacho-Díaz, B., García-Botello, D.R., Wegman-Ostrosky, T., Ortiz-Sánchez, E., Herrera-Montalvo, L.A. (2021). Tumor Microenvironment: Comparison Between Primary Origin Tumors and Corresponding Brain Metastasis. In: Monroy-Sosa, A., Chakravarthi, S.S., de la Garza-Salazar, J.G., Meneses Garcia, A., Kassam, A.B. (eds) Principles of Neuro-Oncology. Springer, Cham. https://doi.org/10.1007/978-3-030-54879-7_3

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