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Breast Disease pp 541-552 | Cite as

Immunotherapy in Breast Cancer

  • Soley Bayraktar
Chapter

Abstract

Immunotherapy for the treatment of breast cancer can be categorized as either (a) specific stimulation of the immune system by active immunization with cancer vaccines or (b) passive immunization, such as tumor-specific antibodies (including immune modulators) or adoptive cell therapies that inhibit the function of or directly kill tumor cells. In this chapter, we will present current information and future perspectives on immunotherapy in patients with breast cancer, including the prognostic role of tumor-infiltrating lymphocytes, immune signatures, targeted therapies modulating the immune system, and tumor antigen cancer vaccines.

It is clear that the cancer immunosurveillance process indeed exists and potentially acts as an extrinsic tumor suppressor. In addition, the immune system can facilitate tumor progression by sculpting the immunogenic phenotype of tumors as they develop. Cancer immunoediting represents a refinement of the cancer immunosurveillance hypothesis and resolves the complex interaction between the tumor and immune system into three phases: elimination, equilibrium, and escape. Major topics in the field of immunology deserve a response: What do we know about tumor immunogenicity, and how might we therapeutically improve tumor immunogenicity? How can we modulate the response of the immune system? Is there any gene signature predictive of response to immune modulators? The success of future immunotherapy strategies will depend on the identification of additional immunogenic antigens that can serve as the best tumor rejection targets. Therapeutic success will depend on developing the best antigen delivery systems and on the elucidation of the entire network of immune signaling pathways that regulate immune responses in the tumor microenvironment.

Keywords

Immunotherapy  Cancer vaccine  Breast cancer  Immunoediting  Immune checkpoints  Immunogenicity  Triple-negative breast cancer 

References

  1. 1.
    Disis ML. Immune regulation of cancer. J Clin Oncol. 2010;28(29):4531–8.PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science. 2011;331(6024):1565–70.PubMedCrossRefGoogle Scholar
  3. 3.
    Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD. Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol. 2002;3(11):991–8.PubMedCrossRefGoogle Scholar
  4. 4.
    Burnet FM. The concept of immunological surveillance. Prog Exp Tumor Res. 1970;13:1–27.PubMedCrossRefGoogle Scholar
  5. 5.
    Pusztai L, Karn T, Safonov A, Abu-Khalaf MM, Bianchini G. New strategies in breast cancer: immunotherapy. Clin Cancer Res. 2016;22(9):2105–10.PubMedCrossRefGoogle Scholar
  6. 6.
    Redig AJ, Janne PA. Basket trials and the evolution of clinical trial design in an era of genomic medicine. J Clin Oncol. 2015;33(9):975–7.PubMedCrossRefGoogle Scholar
  7. 7.
    Rooney MS, Shukla SA, Wu CJ, Getz G, Hacohen N. Molecular and genetic properties of tumors associated with local immune cytolytic activity. Cell. 2015;160(1-2):48–61.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Ceeraz S, Nowak EC, Noelle RJ. B7 family checkpoint regulators in immune regulation and disease. Trends Immunol. 2013;34(11):556–63.PubMedCrossRefGoogle Scholar
  9. 9.
    Topalian SL, Drake CG, Pardoll DM. Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer Cell. 2015;27(4):450–61.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Jung K, Choi I. Emerging co-signaling networks in T Cell immune regulation. Immune Netw. 2013;13(5):184–93.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Tripathi S, Guleria I. Role of PD1/PDL1 pathway, and TH17 and treg cells in maternal tolerance to the fetus. Biom J. 2015;38(1):25–31.Google Scholar
  12. 12.
    Pentcheva-Hoang T, Corse E, Allison JP. Negative regulators of T-cell activation: potential targets for therapeutic intervention in cancer, autoimmune disease, and persistent infections. Immunol Rev. 2009;229(1):67–87.PubMedCrossRefGoogle Scholar
  13. 13.
    Fife BT, Bluestone JA. Control of peripheral T-cell tolerance and autoimmunity via the CTLA-4 and PD-1 pathways. Immunol Rev. 2008;224:166–82.PubMedCrossRefGoogle Scholar
  14. 14.
    Vonderheide RH, LoRusso PM, Khalil M, Gartner EM, Khaira D, Soulieres D, 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(13):3485–94.PubMedCrossRefGoogle Scholar
  15. 15.
    McArthur HL, Diab A, Page DB, Yuan J, Solomon SB, Sacchini V, et al. A pilot study of preoperative single-dose Ipilimumab and/or Cryoablation in women with early-stage breast cancer with comprehensive immune profiling. Clin Cancer Res. 2016;22(23):5729–37.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Butte MJ, Keir ME, Phamduy TB, Sharpe AH, Freeman GJ. Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses. Immunity. 2007;27(1):111–22.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med. 2000;192(7):1027–34.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Latchman Y, Wood CR, Chernova T, Chaudhary D, Borde M, Chernova I, et al. PD-L2 is a second ligand for PD-1 and inhibits T cell activation. Nat Immunol. 2001;2(3):261–8.PubMedCrossRefGoogle Scholar
  19. 19.
    Zinselmeyer BH, Heydari S, Sacristan C, Nayak D, Cammer M, Herz J, et al. PD-1 promotes immune exhaustion by inducing antiviral T cell motility paralysis. J Exp Med. 2013;210(4):757–74.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Honda T, Egen JG, Lammermann T, Kastenmuller W, Torabi-Parizi P, Germain RN. Tuning of antigen sensitivity by T cell receptor-dependent negative feedback controls T cell effector function in inflamed tissues. Immunity. 2014;40(2):235–47.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Vibhakar R, Juan G, Traganos F, Darzynkiewicz Z, Finger LR. Activation-induced expression of human programmed death-1 gene in T-lymphocytes. Exp Cell Res. 1997;232(1):25–8.PubMedCrossRefGoogle Scholar
  22. 22.
    Zielinski C, Knapp S, Mascaux C, Hirsch F. Rationale for targeting the immune system through checkpoint molecule blockade in the treatment of non-small-cell lung cancer. Ann Oncol. 2013;24(5):1170–9.PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Sabatier R, Finetti P, Mamessier E, Adelaide J, Chaffanet M, Ali HR, et al. Prognostic and predictive value of PDL1 expression in breast cancer. Oncotarget. 2015;6(7):5449–64.PubMedCrossRefGoogle Scholar
  24. 24.
    Hamanishi J, Mandai M, Iwasaki M, Okazaki T, Tanaka Y, Yamaguchi K, et al. Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer. Proc Natl Acad Sci U S A. 2007;104(9):3360–5.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    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(3):667–76.PubMedCrossRefGoogle Scholar
  26. 26.
    Mittendorf EA, Philips AV, Meric-Bernstam F, Qiao N, Wu Y, Harrington S, et al. PD-L1 expression in triple-negative breast cancer. Cancer Immunol Res. 2014;2(4):361–70.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Iwai Y, Ishida M, Tanaka Y, Okazaki T, Honjo T, Minato N. Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl Acad Sci U S A. 2002;99(19):12293–7.PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Kodumudi KN, Siegel J, Weber AM, Scott E, Sarnaik AA, Pilon-Thomas S. Immune checkpoint blockade to improve tumor infiltrating lymphocytes for adoptive cell therapy. PLoS One. 2016;11(4):e0153053.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Sotiriou C, Pusztai L. Gene-expression signatures in breast cancer. N Engl J Med. 2009;360(8):790–800.PubMedCrossRefGoogle Scholar
  30. 30.
    Reis-Filho JS, Weigelt B, Fumagalli D, Sotiriou C. Molecular profiling: moving away from tumor philately. Sci Transl Med. 2010;2(47):47ps3.CrossRefGoogle Scholar
  31. 31.
    Finak G, Bertos N, Pepin F, Sadekova S, Souleimanova M, Zhao H, et al. Stromal gene expression predicts clinical outcome in breast cancer. Nat Med. 2008;14(5):518–27.PubMedCrossRefGoogle Scholar
  32. 32.
    Ignatiadis M, Singhal SK, Desmedt C, Haibe-Kains B, Criscitiello C, Andre F, et al. Gene modules and response to neoadjuvant chemotherapy in breast cancer subtypes: a pooled analysis. J Clin Oncol. 2012;30(16):1996–2004.PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Desmedt C, Haibe-Kains B, Wirapati P, Buyse M, Larsimont D, Bontempi G, et al. Biological processes associated with breast cancer clinical outcome depend on the molecular subtypes. Clin Cancer Res. 2008;14(16):5158–65.PubMedCrossRefGoogle Scholar
  34. 34.
    Schmidt M, Bohm D, von Torne C, Steiner E, Puhl A, Pilch H, et al. The humoral immune system has a key prognostic impact in node-negative breast cancer. Cancer Res. 2008;68(13):5405–13.PubMedCrossRefGoogle Scholar
  35. 35.
    Teschendorff AE, Miremadi A, Pinder SE, Ellis IO, Caldas C. An immune response gene expression module identifies a good prognosis subtype in estrogen receptor negative breast cancer. Genome Biol. 2007;8(8):R157.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Bianchini G, Qi Y, Alvarez RH, Iwamoto T, Coutant C, Ibrahim NK, et al. Molecular anatomy of breast cancer stroma and its prognostic value in estrogen receptor-positive and -negative cancers. J Clin Oncol. 2010;28(28):4316–23.PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    Callari M, Cappelletti V, D’Aiuto F, Musella V, Lembo A, Petel F, et al. Subtype-specific Metagene-based prediction of outcome after neoadjuvant and adjuvant treatment in breast cancer. Clin Cancer Res. 2016;22(2):337–45.PubMedCrossRefGoogle Scholar
  38. 38.
    DeNardo DG, Coussens LM. Inflammation and breast cancer. Balancing immune response: crosstalk between adaptive and innate immune cells during breast cancer progression. Breast Cancer Res. 2007;9(4):212.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Denkert C, von Minckwitz G, Brase JC, Sinn BV, Gade S, Kronenwett R, et al. Tumor-infiltrating lymphocytes and response to neoadjuvant chemotherapy with or without carboplatin in human epidermal growth factor receptor 2-positive and triple-negative primary breast cancers. J Clin Oncol. 2015;33(9):983–91.CrossRefGoogle Scholar
  40. 40.
    Mahmoud SM, Paish EC, Powe DG, Macmillan RD, Grainge MJ, Lee AH, et al. Tumor-infiltrating CD8+ lymphocytes predict clinical outcome in breast cancer. J Clin Oncol. 2011;29(15):1949–55.PubMedCrossRefGoogle Scholar
  41. 41.
    Ruffell B, Au A, Rugo HS, Esserman LJ, Hwang ES, Coussens LM. Leukocyte composition of human breast cancer. Proc Natl Acad Sci U S A. 2012;109(8):2796–801.PubMedCrossRefGoogle Scholar
  42. 42.
    Dedeurwaerder S, Desmedt C, Calonne E, Singhal SK, Haibe-Kains B, Defrance M, et al. DNA methylation profiling reveals a predominant immune component in breast cancers. EMBO Mol Med. 2011;3(12):726–41.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Andre F, Job B, Dessen P, Tordai A, Michiels S, Liedtke C, et al. Molecular characterization of breast cancer with high-resolution oligonucleotide comparative genomic hybridization array. Clin Cancer Res. 2009;15(2):441–51.PubMedCrossRefGoogle Scholar
  44. 44.
    Desmedt C, Di Leo A, de Azambuja E, Larsimont D, Haibe-Kains B, Selleslags J, et al. Multifactorial approach to predicting resistance to anthracyclines. J Clin Oncol. 2011;29(12):1578–86.PubMedCrossRefGoogle Scholar
  45. 45.
    Issa-Nummer Y, Darb-Esfahani S, Loibl S, Kunz G, Nekljudova V, Schrader I, et al. Prospective validation of immunological infiltrate for prediction of response to neoadjuvant chemotherapy in HER2-negative breast cancer--a substudy of the neoadjuvant GeparQuinto trial. PLoS One. 2013;8(12):e79775.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Zitvogel L, Apetoh L, Ghiringhelli F, Kroemer G. Immunological aspects of cancer chemotherapy. Nat Rev Immunol. 2008;8(1):59–73.PubMedCrossRefGoogle Scholar
  47. 47.
    Galluzzi L, Senovilla L, Zitvogel L, Kroemer G. The secret ally: immunostimulation by anticancer drugs. Nat Rev Drug Discov. 2012;11(3):215–33.PubMedCrossRefGoogle Scholar
  48. 48.
    Dieci MV, Mathieu MC, Guarneri V, Conte P, Delaloge S, Andre F, et al. Prognostic and predictive value of tumor-infiltrating lymphocytes in two phase III randomized adjuvant breast cancer trials. Ann Oncol. 2015;26(8):1698–704.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Sabatier R, Finetti P, Cervera N, Lambaudie E, Esterni B, Mamessier E, et al. A gene expression signature identifies two prognostic subgroups of basal breast cancer. Breast Cancer Res Treat. 2011;126(2):407–20.PubMedCrossRefGoogle Scholar
  50. 50.
    Salgado R, Denkert C, Demaria S, Sirtaine N, Klauschen F, Pruneri G, et al. The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014. Ann Oncol. 2015;26(2):259–71.PubMedCrossRefGoogle Scholar
  51. 51.
    DeNardo DG, Barreto JB, Andreu P, Vasquez L, Tawfik D, Kolhatkar N, et al. CD4(+) T cells regulate pulmonary metastasis of mammary carcinomas by enhancing protumor properties of macrophages. Cancer Cell. 2009;16(2):91–102.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Bidwell BN, Slaney CY, Withana NP, Forster S, Cao Y, Loi S, et al. Silencing of Irf7 pathways in breast cancer cells promotes bone metastasis through immune escape. Nat Med. 2012;18(8):1224–31.PubMedCrossRefGoogle Scholar
  53. 53.
    Mittendorf EA, Peoples GE, Singletary SE. Breast cancer vaccines: promise for the future or pipe dream? Cancer. 2007;110(8):1677–86.PubMedCrossRefGoogle Scholar
  54. 54.
    Musolino A, Naldi N, Bortesi B, Pezzuolo D, Capelletti M, Missale G, 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(11):1789–96.PubMedCrossRefGoogle Scholar
  55. 55.
    Tamura K, Shimizu C, Hojo T, Akashi-Tanaka S, Kinoshita T, Yonemori K, et al. FcgammaR2A and 3A polymorphisms predict clinical outcome of trastuzumab in both neoadjuvant and metastatic settings in patients with HER2-positive breast cancer. Ann Oncol. 2011;22(6):1302–7.PubMedCrossRefGoogle Scholar
  56. 56.
    Rakhra K, Bachireddy P, Zabuawala T, Zeiser R, Xu L, Kopelman A, et al. CD4(+) T cells contribute to the remodeling of the microenvironment required for sustained tumor regression upon oncogene inactivation. Cancer Cell. 2010;18(5):485–98.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Goodman AM, Kato S, Bazhenova L, Patel SP, Frampton GM, Miller V, et al. Tumor mutational burden as an independent predictor of response to immunotherapy in diverse cancers. Mol Cancer Ther. 2017;16(11):2598–608.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Bonta I, Isac JF, Meiri E, Bonta D, et al. Correlation between tumor mutation burden and response to immunotherapy. ASCO 2017 Annual Meeting; Chicago: J Clin Oncol. 2017.Google Scholar
  59. 59.
    Barroso-Sousa R JE, Kim D, et al. Determinants of high tumor mutational burden (TMB) and mutational signatures in breast cancer. ASCO Annual Meeting; Chicago: J Clin Oncol. 2018.Google Scholar
  60. 60.
    Xu J, Guo X, Jing M, Sun T. Prediction of tumor mutation burden in breast cancer based on the expression of ER, PR, HER-2, and Ki-67. Onco Targets Ther. 2018;11:2269–75.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Gettinger S, Horn L, Jackman D, Spigel D, Antonia S, Hellmann M, et al. Five-year follow-up of Nivolumab in previously treated advanced non-small-cell lung cancer: results from the CA209-003 study. J Clin Oncol. 2018:JCO2017770412.Google Scholar
  62. 62.
    Vokes EE, Ready N, Felip E, Horn L, Burgio MA, Antonia SJ, et al. Nivolumab versus docetaxel in previously treated advanced non-small-cell lung cancer (CheckMate 017 and CheckMate 057): 3-year update and outcomes in patients with liver metastases. Ann Oncol. 2018;29(4):959–65.PubMedCrossRefGoogle Scholar
  63. 63.
    Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S, et al. Nivolumab versus Everolimus in advanced renal-cell carcinoma. N Engl J Med. 2015;373(19):1803–13.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Wolchok JD, Chiarion-Sileni V, Gonzalez R, Rutkowski P, Grob JJ, Cowey CL, et al. Overall survival with combined Nivolumab and Ipilimumab in advanced melanoma. N Engl J Med. 2017;377(14):1345–56.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Wang C, Thudium KB, Han M, Wang XT, Huang H, Feingersh D, et al. In vitro characterization of the anti-PD-1 antibody nivolumab, BMS-936558, and in vivo toxicology in non-human primates. Cancer Immunol Res. 2014;2(9):846–56.PubMedCrossRefGoogle Scholar
  66. 66.
    Champiat S, Ferte C, Lebel-Binay S, Eggermont A, Soria JC. Exomics and immunogenics: bridging mutational load and immune checkpoints efficacy. Oncoimmunology. 2014;3(1):e27817.PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Rosenberg SA. Decade in review-cancer immunotherapy: entering the mainstream of cancer treatment. Nat Rev Clin Oncol. 2014;11(11):630–2.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, et al. PD-1 Blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372(26):2509–20.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Loi S, Sirtaine N, Piette F, Salgado R, Viale G, Van Eenoo F, et al. Prognostic and predictive value of tumor-infiltrating lymphocytes in a phase III randomized adjuvant breast cancer trial in node-positive breast cancer comparing the addition of docetaxel to doxorubicin with doxorubicin-based chemotherapy: BIG 02-98. J Clin Oncol. 2013;31(7):860–7.PubMedCrossRefGoogle Scholar
  70. 70.
    Ali HR, Glont SE, Blows FM, Provenzano E, Dawson SJ, Liu B, et al. PD-L1 protein expression in breast cancer is rare, enriched in basal-like tumours and associated with infiltrating lymphocytes. Ann Oncol. 2015;26(7):1488–93.PubMedCrossRefGoogle Scholar
  71. 71.
    Wimberly H, Brown JR, Schalper K, Haack H, Silver MR, Nixon C, et al. PD-L1 expression correlates with tumor-infiltrating lymphocytes and response to neoadjuvant chemotherapy in breast cancer. Cancer Immunol Res. 2015;3(4):326–32.PubMedCrossRefGoogle Scholar
  72. 72.
    Spranger S, Spaapen RM, Zha Y, Williams J, Meng Y, Ha TT, et al. Up-regulation of PD-L1, IDO, and T(regs) in the melanoma tumor microenvironment is driven by CD8(+) T cells. Sci Transl Med. 2013;5(200):200ra116.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Nanda R, Chow LQ, Dees EC, Berger R, Gupta S, Geva R, et al. Pembrolizumab in patients with advanced triple-negative breast cancer: phase Ib KEYNOTE-012 study. J Clin Oncol. 2016;34(21):2460–7.PubMedCrossRefPubMedCentralGoogle Scholar
  74. 74.
    Dirix LY Takacs I, Nikolinakos P, Jerusalem G, Arkenau H-T, Hamilton EP, von Heydebreck A, Grote H-J, Chin K, Lippman ME. Sint Augustinus. Avelumab (MSB0010718C), an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase Ib JAVELIN solid tumor trial. San Antonio Breast Conference, 2015.Google Scholar
  75. 75.
    Schadendorf D, Hodi FS, Robert C, Weber JS, Margolin K, Hamid O, et al. Pooled analysis of long-term survival data from Phase II and Phase III trials of Ipilimumab in Unresectable or Metastatic Melanoma. J Clin Oncol. 2015;33(17):1889–94.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711–23.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Persson J, Beyer I, Yumul R, Li Z, Kiem HP, Roffler S, et al. Immuno-therapy with anti-CTLA4 antibodies in tolerized and non-tolerized mouse tumor models. PLoS One. 2011;6(7):e22303.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Stagg J, Loi S, Divisekera U, Ngiow SF, Duret H, Yagita H, et al. Anti-ErbB-2 mAb therapy requires type I and II interferons and synergizes with anti-PD-1 or anti-CD137 mAb therapy. Proc Natl Acad Sci U S A. 2011;108(17):7142–7.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Park S, Jiang Z, Mortenson ED, Deng L, Radkevich-Brown O, Yang X, et al. The therapeutic effect of anti-HER2/neu antibody depends on both innate and adaptive immunity. Cancer Cell. 2010;18(2):160–70.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Sakaguchi S, Yamaguchi T, Nomura T, Ono M. Regulatory T cells and immune tolerance. Cell. 2008;133(5):775–87.PubMedCrossRefGoogle Scholar
  81. 81.
    Merlo A, Casalini P, Carcangiu ML, Malventano C, Triulzi T, Menard S, et al. FOXP3 expression and overall survival in breast cancer. J Clin Oncol. 2009;27(11):1746–52.PubMedCrossRefGoogle Scholar
  82. 82.
    Kanjanapan Y DD, Wang L, et al. ASCO Annual Meeting; Chicago: J Clin Oncol; 2018.Google Scholar
  83. 83.
    Hamm CA, Moran D, Rao K, Trusk PB, Pry K, Sausen M, et al. Genomic and immunological tumor profiling identifies targetable pathways and extensive CD8+/PDL1+ immune infiltration in inflammatory breast cancer tumors. Mol Cancer Ther. 2016;15(7):1746–56.PubMedCrossRefGoogle Scholar
  84. 84.
    Bertucci F, Finetti P, Colpaert C, Mamessier E, Parizel M, Dirix L, et al. PDL1 expression in inflammatory breast cancer is frequent and predicts for the pathological response to chemotherapy. Oncotarget. 2015;6(15):13506–19.PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Recchia F, et al. Maintenance immunotherapy in patients with metastatic breast cancer (MBC) who have a clinical benefit with chemotherapy. Long-term follow-up of a phase II study. ASCO Annual Meeting; Chicago: J Clin Oncol; 2018.CrossRefGoogle Scholar
  86. 86.
    Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, et al. Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. N Engl J Med. 2017;377(20):1919–29.PubMedCrossRefGoogle Scholar
  87. 87.
    Criscitiello C. Tumor-associated antigens in breast cancer. Breast Care (Basel). 2012;7(4):262–6.CrossRefGoogle Scholar
  88. 88.
    Emens LA. Chemotherapy and tumor immunity: an unexpected collaboration. Front Biosci. 2008;13:249–57.PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Emens LA, Jaffee EM. Leveraging the activity of tumor vaccines with cytotoxic chemotherapy. Cancer Res. 2005;65(18):8059–64.PubMedCrossRefGoogle Scholar
  90. 90.
    Ma W, Gilligan BM, Yuan J, Li T. Current status and perspectives in translational biomarker research for PD-1/PD-L1 immune checkpoint blockade therapy. J Hematol Oncol. 2016;9(1):47.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Loi S, Dushyanthen S, Beavis PA, Salgado R, Denkert C, Savas P, et al. RAS/MAPK activation is associated with reduced tumor-infiltrating lymphocytes in triple-negative breast cancer: therapeutic cooperation between MEK and PD-1/PD-L1 immune checkpoint inhibitors. Clin Cancer Res. 2016;22(6):1499–509.PubMedCrossRefGoogle Scholar
  92. 92.
    Leisha A, Emens FSB, Cassier P. Inhibition of PD-L1 by MPDL3280A leads to clinical activity in patients with metastatic triple-negative breast cancer (TNBC). Philadelphia: American Association of Cancer Research; 2015. Abstract 2859.Google Scholar
  93. 93.
    Adams S, Diamond J, Hamilton E, et al. Phase Ib trial of atezolizumab in combination with nab-paclitaxel in patients with metastatic triple-negative breast cancer (mTNBC). Presented at: American Society of Clinical Oncology annual meeting. Chicago, Illinois. June 2016. Abstract 1009.Google Scholar
  94. 94.
    Brignone C, Gutierrez M, Mefti F, et al. First-line chemoimmunotherapy in metastatic breast carcinoma: combination of paclitaxel and IMP321 (LAG-3Ig) enhances immune responses and antitumor activity. J Transl Med. 2010;8:71.PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Rugo HS, Delord J-P, Im S-A, et al. Preliminary efficacy and safety of pembrolizumab (MK-3475) in patients with PD-L1-positive, estrogen receptor-positive (ER+)/HER2-negative advanced breast cancer enrolled in KEYNOTE-028 [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium; 2015 Dec 6–10; San Antonio, TX. Philadelphia (PA): American Association for Cancer Research; 2015. Abstract nr S5–07.Google Scholar
  96. 96.
    Emens LA. Breast cancer immunobiology driving immunotherapy: vaccines and immune checkpoint blockade. Expert Rev Anticancer Ther. 2012;12:1597–611.PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Tiriveedhi V, Tucker N, Herndon J, et al. Safety and preliminary evidence of biologic efficacy of a mammaglobin-a DNA vaccine in patients with stable metastatic breast cancer. Clin Cancer Res. 2014;20:5964–75.PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Miles D, Roché H, Martin M, et al. Theratope Study Group. Phase III multicenter clinical trial of the sialyl-TN (STn)-keyhole limpet hemocyanin (KLH) vaccine for metastatic breast cancer. Oncologist. 2011;16:1092–100.PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Svane IM, Pedersen AE, Johansen JS, et al. Vaccination with p53 peptide-pulsed dendritic cells is associated with disease stabilization in patients with p53 expressing advanced breast cancer: monitoring of serum YKL-40 and IL-6 as response biomarkers. Cancer Immunol Immunother. 2007;56:1485–99.PubMedCrossRefGoogle Scholar
  100. 100.
    Chen G, Gupta R, Petrik S, et al. A feasibility study of cyclophosphamide, trastuzumab, and an allogeneic GM-CSF-secreting tumor vaccine for HER-2+ metastatic breast cancer. Cancer Immunol Res. 2014;2:949–61.PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    Schmid P, Adams S, Rugo HS, Schneeweiss A, Barrios CH, Iwata H, et al. Atezolizumab and Nab-Paclitaxel in advanced triple-negative breast cancer. N Engl J Med. 2018;  https://doi.org/10.1056/NEJMoa1809615.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Soley Bayraktar
    • 1
  1. 1.Memorial Cancer Center, Piyalepaşa Bulvarı, Okmeydanı/ŞişliİstanbulTurkey

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