Gaceta Médica de México

Contenido por año, Vol. y Num.

Índice de este artículo

Información General

Instrucciones para Autores

Mensajes al Editor


>Revistas >Gaceta Médica de México >Año 2017, No. 2

García-Romo GS, García-Castillo KG, Díaz-Rodríguez Á, Reyes-Hernández D, Pedroza-González A
Principales mecanismos inmunorreguladores que favorecen el desarrollo del cáncer de mama
Gac Med Mex 2017; 153 (2)

Idioma: Español
Referencias bibliográficas: 133
Paginas: 229-237
Archivo PDF: 132.44 Kb.

Texto completo


A pesar de los avances hechos en los últimos años en el diagnóstico temprano y los tratamientos, el cáncer de mama continúa siendo el de mayor frecuencia y mortalidad en las mujeres de todo el mundo. Terapias alternativas como la inmunoterapia se han evaluado en ensayos clínicos, pero han demostrado una eficacia limitada. El fracaso de la inmunoterapia puede estar relacionado con mecanismos inmunosupresores presentes en el microambiente tumoral. En consecuencia, para el desarrollo de nuevas estrategias terapéuticas basadas en inmunoterapia es muy importante entender los mecanismos inmunorreguladores presentes en los tumores mamarios. En esta revisión se discuten algunos de los mecanismos inmunorreguladores descritos en el cáncer de mama.

Palabras clave: Cáncer de mama, Inmunoterapia, Inmunorregulación, Inmunosupresión.


  1. WHO. Global Health Estimates: Deaths by Cause, Age, Sex and Country, 2000-2012. Geneva, World Health Organization, 2014.

  2. Ferlay J, Soerjomataram I, Ervik M, et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013. Available from: http://globocan.iarc.fr

  3. Viale G. The current state of breast cancer classification. Ann Oncol. 2012;23(Suppl 10): X207-10.

  4. González-Angulo AM, Hennessy BT, Broglio K, et al. Trends for inflammatory breast cancer: is survival improving? Oncologist. 2007;12:904-12.

  5. Cristofanilli M, Valero V, Buzdar AU, et al. Inflammatory breast cancer (IBC) and patterns of recurrence: understanding the biology of a unique disease. Cancer. 2007;110:1436-44.

  6. Zardavas D, Irrthum A, Swanton C, Piccart M. Clinical management of breast cancer heterogeneity. Nat Rev Clin Oncol. 2015;12:381-94.

  7. Perou CM, Sorlie T, Eisen MB, et al. Molecular portraits of human breast tumours. Nature. 2000;406:747-52.

  8. Santa-María CA, Gradishar WJ. Changing treatment paradigms in metastatic breast cancer: lessons learned. JAMA Oncol. 2015;1:528-34.

  9. Lasso Varela A, Cobos Campos R, Alia Ramos A. Recurrencias loco-regionales en pacientes con cáncer de mama invasivo que presentan 3 ganglios positivos o menos. ¿Está indicada la radioterapia? Clínica e Investigación en Ginecología y Obstetricia. 2012;39:203-9.

  10. Spector NL, Blackwell KL. Understanding the mechanisms behind trastuzumab therapy for human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol. 2009;27:5838-47.

  11. Ravelli A, Reuben JM, Lanza F, et al. Immune-related strategies driving immunotherapy in breast cancer treatment: a real clinical opportunity. Expert Rev Anticancer Ther. 2015;15:689-702.

  12. Ernst B, Anderson KS. Immunotherapy for the treatment of breast cancer. Curr Oncol Rep. 2015;17:5.

  13. Finn OJ. Cancer immunology. N Engl J Med. 2008;358:2704-15.

  14. Criscitiello C. Tumor-associated antigens in breast cancer. Breast Care (Basel). 2012;7:262-6.

  15. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987;235:177-82.

  16. McKeage K, Perry CM. Trastuzumab: a review of its use in the treatment of metastatic breast cancer overexpressing HER2. Drugs. 2002;62:209-43.

  17. Maly JJ, Macrae ER. Pertuzumab in combination with trastuzumab and chemotherapy in the treatment of HER2-positive metastatic breast cancer: safety, efficacy, and progression free survival. Breast Cancer (Auckl). 2014;8:81-8.

  18. Nahta R, Hung MC, Esteva FJ. The HER-2-targeting antibodies trastuzumab and pertuzumab synergistically inhibit the survival of breast cancer cells. Cancer Res. 2004;64:2343-6.

  19. Baselga J, Swain SM. Novel anticancer targets: revisiting ERBB2 and discovering ERBB3. Nat Rev Cancer. 2009;9:463-75.

  20. Franklin MC, Carey KD, Vajdos FF, Leahy DJ, de Vos AM, Sliwkowski MX. Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex. Cancer Cell. 2004;5:317-28.

  21. Gianni L, Pienkowski T, Im YH, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012;13:25-32.

  22. Verma S, Miles D, Gianni L, et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med. 2012;367:1783-91.

  23. Lewis Phillips GD, Li G, Dugger DL, et al. Targeting HER2-positive breast cancer with trastuzumab-DM1, an antibody-cytotoxic drug conjugate. Cancer Res. 2008;68:9280-90.

  24. Musolino A, Naldi N, Bortesi B, et al. Immunoglobulin G fragment C receptor polymorphisms and clinical efficacy of trastuzumab-based therapy in patients with HER-2/neu-positive metastatic breast cancer. J Clin Oncol. 2008;26:1789-96.

  25. Muraro E, Martorelli D, Turchet E, et al. A different immunologic profile characterizes patients with HER-2-overexpressing and HER-2-negative locally advanced breast cancer: implications for immune-based therapies. Breast Cancer Res. 2011;13:R117.

  26. Perez EA, Thompson EA, Ballman KV, et al. Genomic analysis reveals that immune function genes are strongly linked to clinical outcome in the North Central Cancer Treatment Group n9831 Adjuvant Trastuzumab Trial. J Clin Oncol. 2015;33:701-8.

  27. Kiewe P, Hasmuller S, Kahlert S, et al. Phase I trial of the trifunctional anti-HER2 x anti-CD3 antibody ertumaxomab in metastatic breast cancer. Clin Cancer Res. 2006;12:3085-91.

  28. Huang Y, Ma C, Zhang Q, et al. CD4+ and CD8+ T cells have opposing roles in breast cancer progression and outcome. Oncotarget. 2015;6:17462-78.

  29. Aspord C, Pedroza-González A, Gallegos M, et al. Breast cancer instructs dendritic cells to prime interleukin 13-secreting CD4+ T cells that facilitate tumor development. J Exp Med. 2007;204:1037-47.

  30. Faghih Z, Erfani N, Haghshenas MR, Safaei A, Talei AR, Ghaderi A. Immune profiles of CD4+ lymphocyte subsets in breast cancer tumor draining lymph nodes. Immunol Lett. 2014;158:57-65.

  31. Li B, Li Y, Wang XY, et al. Profile of differentially expressed intratumoral cytokines to predict the immune-polarizing side effects of tamoxifen in breast cancer treatment. Am J Cancer Res. 2015;5:726-37.

  32. Terabe M, Matsui S, Noben-Trauth N, et al. NKT cell-mediated repression of tumor immunosurveillance by IL-13 and the IL-4R-STAT6 pathway. Nat Immunol. 2000;1:515-20.

  33. Park JM, Terabe M, Donaldson DD, Forni G, Berzofsky JA. Natural immunosurveillance against spontaneous, autochthonous breast cancers revealed and enhanced by blockade of IL-13-mediated negative regulation. Cancer Immunol Immunother. 2008;57:907-12.

  34. Faghih Z, Rezaeifard S, Safaei A, Ghaderi A, Erfani N. IL-17 and IL-4 producing CD8+ T cells in tumor draining lymph nodes of breast cancer patients: positive association with tumor progression. Iran J Immunol. 2013;10:193-204.

  35. Zhang WJ, Li BH, Yang XZ, et al. IL-4-induced Stat6 activities affect apoptosis and gene expression in breast cancer cells. Cytokine. 2008;42:39-47.

  36. Srabovici N, Mujagic Z, Mujanovic-Mustedanagic J, Muminovic Z, Softic A, Begic L. Interleukin 13 expression in the primary breast cancer tumour tissue. Biochem Med (Zagreb). 2011;21:131-8.

  37. Luboshits G, Shina S, Kaplan O, et al. Elevated expression of the CC chemokine regulated on activation, normal T cell expressed and secreted (RANTES) in advanced breast carcinoma. Cancer Res. 1999;59:4681- 7.

  38. Yaal-Hahoshen N, Shina S, Leider-Trejo L, et al. The chemokine CCL5 as a potential prognostic factor predicting disease progression in stage II breast cancer patients. Clin Cancer Res. 2006;12:4474-80.

  39. Niwa Y, Akamatsu H, Niwa H, Sumi H, Ozaki Y, Abe A. Correlation of tissue and plasma RANTES levels with disease course in patients with breast or cervical cancer. Clin Cancer Res. 2001;7:285-9.

  40. Zhang Q, Qin J, Zhong L, et al. CCL5-mediated Th2 immune polarization promotes metastasis in luminal breast cancer. Cancer Res. 2015;75:4312-21.

  41. Wu TC, Xu K, Banchereau R, et al. Reprogramming tumor-infiltrating dendritic cells for CD103+ CD8+ mucosal T-cell differentiation and breast cancer rejection. Cancer Immunol Res. 2014;2:487-500.

  42. Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science. 2003;299:1057-61.

  43. Sakaguchi S, Yamaguchi T, Nomura T, Ono M. Regulatory T cells and immune tolerance. Cell. 2008;133:775-87.

  44. Kim S, Lee A, Lim W, et al. Zonal difference and prognostic significance of foxp3 regulatory T cell infiltration in breast cancer. J Breast Cancer. 2014;17:8-17.

  45. Takenaka M, Seki N, Toh U, et al. FOXP3 expression in tumor cells and tumor-infiltrating lymphocytes is associated with breast cancer prognosis. Mol Clin Oncol. 2013;1:625-32.

  46. Lee S, Cho EY, Park YH, Ahn JS, Im YH. Prognostic impact of FOXP3 expression in triple-negative breast cancer. Acta Oncol. 2013;52:73-81.

  47. Pedroza-González A, Verhoef C, Ijzermans JN, et al. Activated tumor-infiltrating CD4+ regulatory T cells restrain antitumor immunity in patients with primary or metastatic liver cancer. Hepatology. 2013;57:183-94.

  48. Tang Y, Xu X, Guo S, et al. An increased abundance of tumor-infiltrating regulatory T cells is correlated with the progression and prognosis of pancreatic ductal adenocarcinoma. PLoS One. 2014;9:e91551.

  49. Schmidt HH, Ge Y, Hartmann FJ, et al. HLA class II tetramers reveal tissue-specific regulatory T cells that suppress T-cell responses in breast carcinoma patients. Oncoimmunology. 2013;2:e24962.

  50. Weiss VL, Lee TH, Song H, et al. Trafficking of high avidity HER-2/ neu-specific T cells into HER-2/neu-expressing tumors after depletion of effector/memory-like regulatory T cells. PLoS One. 2012;7:e31962.

  51. Wang ZK, Yang B, Liu H, et al. Regulatory T cells increase in breast cancer and in stage IV breast cancer. Cancer Immunol Immunother. 2012;61:911-6.

  52. Gobert M, Treilleux I, Bendriss-Vermare N, et al. Regulatory T cells recruited through CCL22/CCR4 are selectively activated in lymphoid infiltrates surrounding primary breast tumors and lead to an adverse clinical outcome. Cancer Res. 2009;69:2000-9.

  53. Sisirak V, Faget J, Gobert M, et al. Impaired IFN-alpha production by plasmacytoid dendritic cells favors regulatory T-cell expansion that may contribute to breast cancer progression. Cancer Res. 2012;72:5188-97.

  54. Krausz LT, Fischer-Fodor E, Major ZZ, Fetica B. GITR-expressing regulatory T-cell subsets are increased in tumor-positive lymph nodes from advanced breast cancer patients as compared to tumor-negative lymph nodes. Int J Immunopathol Pharmacol. 2012;25:59-66.

  55. Le Mercier I, Poujol D, Sanlaville A, et al. Tumor promotion by intratumoral plasmacytoid dendritic cells is reversed by TLR7 ligand treatment. Cancer Res. 2013;73:4629-40.

  56. Pedroza-González A, Kwekkeboom J, Sprengers D. T-cell suppression mediated by regulatory T cells infiltrating hepatic tumors can be overcome by GITRL treatment. Oncoimmunology. 2013;2:e22450.

  57. Pedroza-González A, Zhou G, Singh SP, et al. GITR engagement in combination with CTLA-4 blockade completely abrogates immunosuppression mediated by human liver tumor-derived regulatory T cells ex vivo. OncoImmunology. 2015;4:e1051297.

  58. Vonderheide RH, LoRusso PM, Khalil M, et al. Tremelimumab in combination with exemestane in patients with advanced breast cancer and treatment-associated modulation of inducible costimulator expression on patient T cells. Clin Cancer Res. 2010;16:3485-94.

  59. Lu L, Xu X, Zhang B, Zhang R, Ji H, Wang X. Combined PD-1 blockade and GITR triggering induce a potent antitumor immunity in murine cancer models and synergizes with chemotherapeutic drugs. J Transl Med. 2014;12:36.

  60. Pruitt SK, Boczkowski D, De Rosa N, et al. Enhancement of anti-tumor immunity through local modulation of CTLA-4 and GITR by dendritic cells. Eur J Immunol. 2011;41:3553-63.

  61. Liu Z, Tian S, Falo LD Jr, Sakaguchi S, You Z. Therapeutic immunity by adoptive tumor-primed CD4(+) T-cell transfer in combination with in vivo GITR ligation. Mol Ther. 2009;17:1274-81.

  62. Liu YJ, Soumelis V, Watanabe N, et al. TSLP: an epithelial cell cytokine that regulates T cell differentiation by conditioning dendritic cell maturation. Annu Rev Immunol. 2007;25:193-219.

  63. Pedroza-González A, Xu K, Wu TC, et al. Thymic stromal lymphopoietin fosters human breast tumor growth by promoting type 2 inflammation. J Exp Med. 2011;208:479-90.

  64. Soumelis V, Reche PA, Kanzler H, et al. Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP. Nat Immunol. 2002;3:673-80.

  65. Hanabuchi S, Ito T, Park WR, et al. Thymic stromal lymphopoietin-activated plasmacytoid dendritic cells induce the generation of FOXP3+ regulatory T cells in human thymus. J Immunol. 2010;184:2999-3007.

  66. Pockaj BA, Basu GD, Pathangey LB, et al. Reduced T-cell and dendritic cell function is related to cyclooxygenase-2 overexpression and prostaglandin E2 secretion in patients with breast cancer. Ann Surg Oncol. 2004;11:328-39.

  67. Gabrilovich DI, Corak J, Ciernik IF, Kavanaugh D, Carbone DP. Decreased antigen presentation by dendritic cells in patients with breast cancer. Clin Cancer Res. 1997;3:483-90.

  68. Sisirak V, Faget J, Vey N, et al. Plasmacytoid dendritic cells deficient in IFNalpha production promote the amplification of FOXP3 regulatory T cells and are associated with poor prognosis in breast cancer patients. Oncoimmunology. 2013;2:e22338.

  69. Faget J, Bendriss-Vermare N, Gobert M, et al. ICOS-ligand expression on plasmacytoid dendritic cells supports breast cancer progression by promoting the accumulation of immunosuppressive CD4+ T cells. Cancer Res. 2012;72:6130-41.

  70. Faget J, Sisirak V, Blay JY, Caux C, Bendriss-Vermare N, Menetrier-Caux C. ICOS is associated with poor prognosis in breast cancer as it promotes the amplification of immunosuppressive CD4 T cells by plasmacytoid dendritic cells. Oncoimmunology. 2013;2:e23185.

  71. Treilleux I, Blay JY, Bendriss-Vermare N, et al. Dendritic cell infiltration and prognosis of early stage breast cancer. Clin Cancer Res. 2004;10:7466-74.

  72. Komohara Y, Fujiwara Y, Ohnishi K, Takeya M. Tumor-associated macrophages: potential therapeutic targets for anti-cancer therapy. Adv Drug Deliv Rev. 2016;99:180-5.

  73. Brady NJ, Chuntova P, Schwertfeger KL. Macrophages: regulators of the inflammatory microenvironment during mammary gland development and breast cancer. Mediators Inflamm. 2016;2016:4549676.

  74. Gwak JM, Jang MH, Kim DI, Seo AN, Park SY. Prognostic value of tumor- associated macrophages according to histologic locations and hormone receptor status in breast cancer. PLoS One. 2015;10:e0125728.

  75. Yuan ZY, Luo RZ, Peng RJ, Wang SS, Xue C. High infiltration of tumor-associated macrophages in triple-negative breast cancer is associated with a higher risk of distant metastasis. Onco Targets Ther. 2014;7:1475-80.

  76. Mahmoud SM, Lee AH, Paish EC, Macmillan RD, Ellis IO, Green AR. Tumour-infiltrating macrophages and clinical outcome in breast cancer. J Clin Pathol. 2012;65:159-63.

  77. Kalinski P, Hilkens CM, Snijders A, Snijdewint FG, Kapsenberg ML. IL-12-deficient dendritic cells, generated in the presence of prostaglandin E2, promote type 2 cytokine production in maturing human naive T helper cells. J Immunol. 1997;159:28-35.

  78. Li H, Yang B, Huang J, et al. Cyclooxygenase-2 in tumor-associated macrophages promotes breast cancer cell survival by triggering a positive- feedback loop between macrophages and cancer cells. Oncotarget. 2015;6:29637-50.

  79. Sousa S, Brion R, Lintunen M, et al. Human breast cancer cells educate macrophages toward the M2 activation status. Breast Cancer Res. 2015;17:101.

  80. Hou Z, Falcone DJ, Subbaramaiah K, Dannenberg AJ. Macrophages induce COX-2 expression in breast cancer cells: role of IL-1beta autoamplification. Carcinogenesis. 2011;32:695-702.

  81. Chanmee T, Ontong P, Konno K, Itano N. Tumor-associated macrophages as major players in the tumor microenvironment. Cancers (Basel). 2014;6:1670-90.

  82. Noy R, Pollard JW. Tumor-associated macrophages: from mechanisms to therapy. Immunity. 2014;41:49-61.

  83. Ostuni R, Kratochvill F, Murray PJ, Natoli G. Macrophages and cancer: from mechanisms to therapeutic implications. Trends Immunol. 2015;36:229-39.

  84. Protti MP, De Monte L. Cross-talk within the tumor microenvironment mediates Th2-type inflammation in pancreatic cancer. Oncoimmunology. 2012;1:89-91.

  85. Hall B, Andreeff M, Marini F. The participation of mesenchymal stem cells in tumor stroma formation and their application as targeted-gene delivery vehicles. Handb Exp Pharmacol. 2007;(180):263-83.

  86. Direkze NC, Hodivala-Dilke K, Jeffery R, et al. Bone marrow contribution to tumor-associated myofibroblasts and fibroblasts. Cancer Res. 2004;64:8492-5.

  87. Kidd S, Spaeth E, Watson K, et al. Origins of the tumor microenvironment: quantitative assessment of adipose-derived and bone marrow-derived stroma. PLoS One. 2012;7:e30563.

  88. Mishra PJ, Mishra PJ, Humeniuk R, et al. Carcinoma-associated fibroblast- like differentiation of human mesenchymal stem cells. Cancer Res. 2008;68:4331-9.

  89. Quante M, Tu SP, Tomita H, et al. Bone marrow-derived myofibroblasts contribute to the mesenchymal stem cell niche and promote tumor growth. Cancer Cell. 2011;19:257-72.

  90. Dvorak HF. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med. 1986;315:1650-9.

  91. Hogan NM, Dwyer RM, Joyce MR, Kerin MJ. Mesenchymal stem cells in the colorectal tumor microenvironment: recent progress and implications. Int J Cancer. 2012;131:1-7.

  92. Karnoub AE, Dash AB, Vo AP, et al. Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature. 2007;449:557-63.

  93. Shinagawa K, Kitadai Y, Tanaka M, et al. Mesenchymal stem cells enhance growth and metastasis of colon cancer. Int J Cancer. 2010;127:2323-33.

  94. Peddareddigari VG, Wang D, Dubois RN. The tumor microenvironment in colorectal carcinogenesis. Cancer Microenviron. 2010;3:149-66.

  95. Hernanda PY, Pedroza-González A, van der Laan LJ, et al. Tumor promotion through the mesenchymal stem cell compartment in human hepatocellular carcinoma. Carcinogenesis. 2013;34:2330-40.

  96. Ma F, Chen D, Chen F, et al. Human umbilical cord mesenchymal stem cells promote breast cancer metastasis by interleukin-8 and interleukin-6 dependent induction of CD44/CD24 cells. Cell Transplant. 2015;24:2585-99.

  97. Di GH, Liu Y, Lu Y, Liu J, Wu C, Duan HF. IL-6 secreted from senescent mesenchymal stem cells promotes proliferation and migration of breast cancer cells. PLoS One. 2014;9:e113572.

  98. Shin SY, Nam JS, Lim Y, Lee YH. TNFalpha-exposed bone marrow-derived mesenchymal stem cells promote locomotion of MDA-MB-231 breast cancer cells through transcriptional activation of CXCR3 ligand chemokines. J Biol Chem. 2010;285:30731-40.

  99. Patel SA, Meyer JR, Greco SJ, Corcoran KE, Bryan M, Rameshwar P. Mesenchymal stem cells protect breast cancer cells through regulatory T cells: role of mesenchymal stem cell-derived TGF-beta. J Immunol. 2010;184:5885-94.

  100. Hodi FS, O’Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363:711-23.

  101. Sznol M, Chen L. Antagonist antibodies to PD-1 and B7-H1 (PD-L1) in the treatment of advanced human cancer. Clin Cancer Res. 2013;19:1021-34.

  102. Nahas GR, Walker ND, Bryan M, Rameshwar P. A perspective of immunotherapy for breast cancer: lessons learned and forward directions for all cancers. Breast Cancer (Auckl). 2015;9(Suppl 2):35-43.

  103. Baroja ML, Vijayakrishnan L, Bettelli E, et al. Inhibition of CTLA-4 function by the regulatory subunit of serine/threonine phosphatase 2A. J Immunol. 2002;168:5070-8.

  104. Tai X, Van Laethem F, Pobezinsky L, et al. Basis of CTLA-4 function in regulatory and conventional CD4(+) T cells. Blood. 2012;119:5155-63.

  105. Ise W, Kohyama M, Nutsch KM, et al. CTLA-4 suppresses the pathogenicity of self antigen-specific T cells by cell-intrinsic and cell-extrinsic mechanisms. Nat Immunol. 2010;11:129-35.

  106. Schneider H, Rudd CE. Diverse mechanisms regulate the surface expression of immunotherapeutic target CTLA-4. Front Immunol. 2014;5:619.

  107. Ishida Y, Agata Y, Shibahara K, Honjo T. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J. 1992;11:3887-95.

  108. Cimino-Mathews A, Thompson E, Taube JM, et al. PD-L1 (B7-H1) expression and the immune tumor microenvironment in primary and metastatic breast carcinomas. Hum Pathol. 2016;47:52-63.

  109. Baptista MZ, Sarian LO, Derchain SF, Pinto GA, Vassallo J. Prognostic significance of PD-L1 and PD-L2 in breast cancer. Hum Pathol. 2016;47:78-84.

  110. Mittendorf EA, Philips AV, Meric-Bernstam F, et al. PD-L1 expression in triple-negative breast cancer. Cancer Immunol Res. 2014;2:361-70.

  111. Mazel M, Jacot W, Pantel K, et al. Frequent expression of PD-L1 on circulating breast cancer cells. Mol Oncol. 2015;9:1773-82.

  112. Park IH, Kong SY, Ro JY, et al. Prognostic implications of tumor-infiltrating lymphocytes in association with programmed death ligand 1 expression in early-stage breast cancer. Clin Breast Cancer. 2016;16:51-8.

  113. Schalper KA. PD-L1 expression and tumor-infiltrating lymphocytes: revisiting the antitumor immune response potential in breast cancer. Oncoimmunology. 2014;3:e29288.

  114. Sabatier R, Finetti P, Mamessier E, et al. Prognostic and predictive value of PDL1 expression in breast cancer. Oncotarget. 2015;6:5449-64.

  115. Muenst S, Schaerli AR, Gao F, et al. Expression of programmed death ligand 1 (PD-L1) is associated with poor prognosis in human breast cancer. Breast Cancer Res Treat. 2014;146:15-24.

  116. Muenst S, Soysal SD, Gao F, Obermann EC, Oertli D, Gillanders WE. The presence of programmed death 1 (PD-1)-positive tumor-infiltrating lymphocytes is associated with poor prognosis in human breast cancer. Breast Cancer Res Treat. 2013;139:667-76.

  117. Chawla A, Philips AV, Alatrash G, Mittendorf E. Immune checkpoints: a therapeutic target in triple negative breast cancer. Oncoimmunology. 2014;3:e28325.

  118. Criscitiello C, Curigliano G. Immunotherapeutics for breast cancer. Curr Opin Oncol. 2013;25:602-8.

  119. Tesniere A, Panaretakis T, Kepp O, et al. Molecular characteristics of immunogenic cancer cell death. Cell Death Differ. 2008;15:3-12.

  120. Sukkurwala AQ, Adjemian S, Senovilla L, et al. Screening of novel immunogenic cell death inducers within the NCI Mechanistic Diversity Set. Oncoimmunology. 2014;3:e28473.

  121. Ghiringhelli F, Apetoh L, Tesniere A, et al. Activation of the NLRP3 inflammasome in dendritic cells induces IL-1beta-dependent adaptive immunity against tumors. Nat Med. 2009;15:1170-8.

  122. Obeid M, Tesniere A, Ghiringhelli F, et al. Calreticulin exposure dictates the immunogenicity of cancer cell death. Nat Med. 2007;13:54-61.

  123. Mattarollo SR, Loi S, Duret H, Ma Y, Zitvogel L, Smyth MJ. Pivotal role of innate and adaptive immunity in anthracycline chemotherapy of established tumors. Cancer Res. 2011;71:4809-20.

  124. Galetto A, Buttiglieri S, Forno S, Moro F, Mussa A, Matera L. Drug- and cell-mediated antitumor cytotoxicities modulate cross-presentation of tumor antigens by myeloid dendritic cells. Anticancer Drugs. 2003;14:833-43.

  125. Carson WE 3rd, Shapiro CL, Crespin TR, Thornton LM, Andersen BL. Cellular immunity in breast cancer patients completing taxane treatment. Clin Cancer Res. 2004;10:3401-9.

  126. Demaria S, Volm MD, Shapiro RL, et al. Development of tumor-infiltrating lymphocytes in breast cancer after neoadjuvant paclitaxel chemotherapy. Clin Cancer Res. 2001;7:3025-30.

  127. Ghiringhelli F, Menard C, Puig PE, et al. Metronomic cyclophosphamide regimen selectively depletes CD4+CD25+ regulatory T cells and restores T and NK effector functions in end stage cancer patients. Cancer Immunol Immunother. 2007;56:641-8.

  128. Chen G, Gupta R, Petrik S, et al. A feasibility study of cyclophosphamide, trastuzumab, and an allogeneic GM-CSF-secreting breast tumor vaccine for HER2+ metastatic breast cancer. Cancer Immunol Res. 2014;2:949-61.

  129. Yamashita-Kashima Y, Iijima S, Yorozu K, et al. Pertuzumab in combination with trastuzumab shows significantly enhanced antitumor activity in HER2-positive human gastric cancer xenograft models. Clin Cancer Res. 2011;17:5060-70.

  130. Kunert A, Straetemans T, Govers C, et al. TCR-engineered T cells meet new challenges to treat solid tumors: choice of antigen, T cell fitness, and sensitization of tumor milieu. Front Immunol. 2013;4:363.

  131. Grupp SA, Kalos M, Barrett D, et al. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med. 2013;368:1509-18.

  132. Kalos M, Levine BL, Porter DL, et al. T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Sci Transl Med. 2011;3:95ra73.

  133. Maus MV, Haas AR, Beatty GL, et al. T cells expressing chimeric antigen receptors can cause anaphylaxis in humans. Cancer Immunol Res. 2013;1:26-31.

>Revistas >Gaceta Médica de México >Año2017, No. 2

· Indice de Publicaciones 
· ligas de Interes 

Derechos Resevados 2019