Immunotherapy for Breast Cancer: Current and Future Strategies (original) (raw)

References

Recently published papers of particular interest have been highlighted as: • Of importance •• Of major importance

  1. McCarthy EF. The toxins of William B. Coley and the treatment of bone and soft-tissue sarcomas. Iowa Orthop J. 2006;26:154–8.
    PubMed PubMed Central Google Scholar
  2. Rosenberg SA, Spiess P, Lafreniere R. A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes. Science. 1986;233(4770):1318–21.
    Article CAS PubMed Google Scholar
  3. •• Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646-674. doi:10.1016/j.cell.2011.02.013. This review highlights the normal and aberrant cellular processes that lead to the development of human cancer from initial genetic changes to metastatic potential.
  4. Couzin-Frankel J. Breakthrough of the year 2013. Cancer immunother Sci. 2013;342(6165):1432–3. doi:10.1126/science.342.6165.1432.
    CAS Google Scholar
  5. •• Porter DL, Levine BL, Kalos M, Bagg A, June CH. Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med. 2011;365(8):725–733. doi:10.1056/NEJMoa1103849. This is the initial descripton of the use of CAR-T cells in a clinical application for CLL, and describes the first-of-its-kind immunotherapy to be FDA approved.
  6. Leach DR, Krummel MF, Allison JP. Enhancement of antitumor immunity by CTLA-4 blockade. Science. 1996;271(5256):1734–6.
    Article CAS PubMed Google Scholar
  7. Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJ, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbe C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A, Urba WJ. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711–23. doi:10.1056/NEJMoa1003466.
    Article CAS PubMed PubMed Central Google Scholar
  8. Robert C, Ribas A, Wolchok JD, Hodi FS, Hamid O, Kefford R, Weber JS, Joshua AM, Hwu WJ, Gangadhar TC, Patnaik A, Dronca R, Zarour H, Joseph RW, Boasberg P, Chmielowski B, Mateus C, Postow MA, Gergich K, Elassaiss-Schaap J, Li XN, Iannone R, Ebbinghaus SW, Kang SP, Daud A. Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. Lancet. 2014;384(9948):1109–17. doi:10.1016/S0140-6736(14)60958-2.
    Article CAS PubMed Google Scholar
  9. Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, Redfern CH, Ferrari AC, Dreicer R, Sims RB, Xu Y, Frohlich MW, Schellhammer PF, Investigators IS. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363(5):411–22. doi:10.1056/NEJMoa1001294.
    Article CAS PubMed Google Scholar
  10. Small EJ, Schellhammer PF, Higano CS, Redfern CH, Nemunaitis JJ, Valone FH, Verjee SS, Jones LA, Hershberg RM. Placebo-controlled phase III trial of immunologic therapy with sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer. J Clin Oncol. 2006;24(19):3089–94. doi:10.1200/JCO.2005.04.5252.
    Article CAS PubMed Google Scholar
  11. Higano CS, Schellhammer PF, Small EJ, Burch PA, Nemunaitis J, Yuh L, Provost N, Frohlich MW. Integrated data from 2 randomized, double-blind, placebo-controlled, phase 3 trials of active cellular immunotherapy with sipuleucel-T in advanced prostate cancer. Cancer. 2009;115(16):3670–9. doi:10.1002/cncr.24429.
    Article CAS PubMed Google Scholar
  12. Porter DL, Kalos M, Zheng Z, Levine B, June C. Chimeric Antigen Receptor Therapy for B-cell Malignancies. J Cancer. 2011;2:331–2.
    Article PubMed PubMed Central Google Scholar
  13. Kalos M, Levine BL, Porter DL, Katz S, Grupp SA, Bagg A, June CH. T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Sci Transl Med. 2011;3(95):95ra73. doi:10.1126/scitranslmed.3002842.
    Article CAS PubMed PubMed Central Google Scholar
  14. 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. doi:10.1186/bcr1746.
    Article PubMed PubMed Central Google Scholar
  15. Jiang X, Shapiro DJ. The immune system and inflammation in breast cancer. Mol Cell Endocrinol. 2014;382(1):673–82. doi:10.1016/j.mce.2013.06.003.
    Article CAS PubMed Google Scholar
  16. Denkert C, Loibl S, Noske A, Roller M, Müller BM, Komor M, Budczies J, Darb-Esfahani S, Kronenwett R, Hanusch C. Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer. J Clin Oncol. 2009;28(1):105–13.
    Article PubMed Google Scholar
  17. Denkert C, Loibl S, Noske A, Roller M, Müller BM, Komor M, Budczies J, Darb-Esfahani S, Kronenwett R, Hanusch C, Cv Törne, Weichert W, Engels K, Solbach C, Schrader I, Dietel M, Gv Minckwitz. Tumor-Associated Lymphocytes As an Independent Predictor of Response to Neoadjuvant Chemotherapy in Breast Cancer. J Clin Oncol. 2010;28(1):105–13. doi:10.1200/jco.2009.23.7370.
    Article CAS PubMed Google Scholar
  18. Bindea G, Mlecnik B, Fridman WH, Galon J. The prognostic impact of anti-cancer immune response: a novel classification of cancer patients. Semin Immunopathol. 2011;33(4):335–40. doi:10.1007/s00281-011-0264-x.
    Article CAS PubMed PubMed Central Google Scholar
  19. Nizar S, Copier J, Meyer B, Bodman-Smith M, Galustian C, Kumar D, Dalgleish A. T-regulatory cell modulation: the future of cancer immunotherapy? Br J Cancer. 2009;100(11):1697–703. doi:10.1038/sj.bjc.6605040.
    Article CAS PubMed PubMed Central Google Scholar
  20. • Comber JD, Philip R. MHC class I antigen presentation and implications for developing a new generation of therapeutic vaccines. Ther Adv Vaccines. 2014;2(3):77–89. doi:10.1177/2051013614525375. This paper highlights the importance of harnessing the immune system’s intrinsic processes, such as intracellular antigen processing, when developing immunotherapies that target a certain action of the immune system.
  21. Muenst S, Schaerli AR, Gao F, Däster S, Trella E, Droeser RA, Muraro MG, Zajac P, Zanetti R, Gillanders WE, Weber WP, Soysal SD. Expression of programmed death ligand 1 (PD-L1) is associated with poor prognosis in human breast cancer. Breast Cancer Res Treat. 2014;146(1):15–24. doi:10.1007/s10549-014-2988-5.
    Article CAS PubMed PubMed Central Google Scholar
  22. Gabrilovich DI, Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol. 2009;9(3):162–74. doi:10.1038/nri2506.
    Article CAS PubMed PubMed Central Google Scholar
  23. Marvel D, Gabrilovich DI. Myeloid-derived suppressor cells in the tumor microenvironment: expect the unexpected. J Clin Invest. 2015;125(9):3356–64. doi:10.1172/JCI80005.
    Article PubMed PubMed Central Google Scholar
  24. Diaz-Montero CM, Salem ML, Nishimura MI, Garrett-Mayer E, Cole DJ, Montero AJ. Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin-cyclophosphamide chemotherapy. Cancer Immunol Immunother. 2009;58(1):49–59. doi:10.1007/s00262-008-0523-4.
    Article CAS PubMed Google Scholar
  25. Zhang S, Ma X, Zhu C, Liu L, Wang G, Yuan X. The role of myeloid-derived suppressor cells in patients with solid tumors: a meta-analysis. PLoS ONE. 2016;11(10):e0164514. doi:10.1371/journal.pone.0164514.
    Article PubMed PubMed Central Google Scholar
  26. Finn OJ. Vaccines for cancer prevention: a practical and feasible approach to the cancer epidemic. Cancer Immunol Res. 2014;2(8):708–13. doi:10.1158/2326-6066.CIR-14-0110.
    Article CAS PubMed PubMed Central Google Scholar
  27. • Mittendorf EA, Clifton GT, Holmes JP, Schneble E, van Echo D, Ponniah S, Peoples GE. Final report of the phase I/II clinical trial of the E75 (nelipepimut-S) vaccine with booster inoculations to prevent disease recurrence in high-risk breast cancer patients. Ann Oncol 25. 2014;25(9):1735–1742. doi:10.1093/annonc/mdu211. An important report demonstrating safety and clinical efficacy of immunotherapy, specifically a breast cancer vaccine, targeting recurrence in high risk patient.
  28. Limentani SA, Campone M, Dorval T, Curigliano G, de Boer R, Vogel C, White S, Bachelot T, Canon JL, Disis M, Awada A, Berliere M, Amant F, Levine E, Burny W, Callegaro A, de Sousa Alves PM, Louahed J, Brichard V, Lehmann FF. A non-randomized dose-escalation Phase I trial of a protein-based immunotherapeutic for the treatment of breast cancer patients with HER2-overexpressing tumors. Breast Cancer Res Treat. 2016;156(2):319–30. doi:10.1007/s10549-016-3751-x.
    Article CAS PubMed Google Scholar
  29. Apostolopoulos V, Pietersz GA, Tsibanis A, Tsikkinis A, Drakaki H, Loveland BE, Piddlesden SJ, Plebanski M, Pouniotis DS, Alexis MN. Pilot phase III immunotherapy study in early-stage breast cancer patients using oxidized mannan-MUC1 [ISRCTN71711835]. Breast Cancer Res. 2006;8(3):R27.
    Article PubMed PubMed Central Google Scholar
  30. Peres Lde P, da Luz FA, Pultz Bdos A, Brigido PC, de Araujo RA, Goulart LR, Silva MJ. Peptide vaccines in breast cancer: The immunological basis for clinical response. Biotechnol Adv. 2015;33(8):1868–77. doi:10.1016/j.biotechadv.2015.10.013.
    Article PubMed Google Scholar
  31. Castilleja A, Carter D, Efferson CL, Ward NE, Kawano K, Fisk B, Kudelka AP, Gershenson DM, Murray JL, O’Brian CA, Ioannides CG. Induction of tumor-reactive CTL by C-side chain variants of the CTL epitope HER-2/neu protooncogene (369-377) selected by molecular modeling of the peptide: HLA-A2 complex. J Immunol. 2002;169(7):3545–54.
    Article CAS PubMed Google Scholar
  32. Milani A, Sangiolo D, Aglietta M, Valabrega G. Recent advances in the development of breast cancer vaccines. Breast Cancer. 2014;6:159–68. doi:10.2147/BCTT.S38428.
    CAS PubMed PubMed Central Google Scholar
  33. Machiels JP, Reilly RT, Emens LA, Ercolini AM, Lei RY, Weintraub D, Okoye FI, Jaffee EM. Cyclophosphamide, doxorubicin, and paclitaxel enhance the antitumor immune response of granulocyte/macrophage-colony stimulating factor-secreting whole-cell vaccines in HER-2/neu tolerized mice. Cancer Res. 2001;61(9):3689–97.
    CAS PubMed Google Scholar
  34. Brusic A, Hainz U, Wadleigh M, Neuberg D, Su M, Canning CM, Deangelo DJ, Stone RM, Lee JS, Mulligan RC, Ritz J, Dranoff G, Sasada T, Wu CJ. Detecting T-cell reactivity to whole cell vaccines: Proof of concept analysis of T-cell response to K562 cell antigens in CML patients. Oncoimmunology. 2012;1(7):1095–103. doi:10.4161/onci.20954.
    Article PubMed PubMed Central Google Scholar
  35. Dillman RO, Beutel LD, Barth NM, de Leon C, O’Connor AA, DePriest C, Nayak SK. Irradiated cells from autologous tumor cell lines as patient-specific vaccine therapy in 125 patients with metastatic cancer: induction of delayed-type hypersensitivity to autologous tumor is associated with improved survival. Cancer Biother Radiopharma. 2002;17(1):51–66.
    Article Google Scholar
  36. Xue D, Liang Y, Duan S, He J, Su J, Zhu J, Hu N, Liu J, Zhao Y, Lu X. Enhanced anti-tumor immunity against breast cancer induced by whole tumor cell vaccines genetically modified expressing alpha-Gal epitopes. Oncol Rep. 2016;36(5):2843–51. doi:10.3892/or.2016.5128.
    Article CAS PubMed Google Scholar
  37. Yang B, Jeang J, Yang A, Wu TC, Hung CF. DNA vaccine for cancer immunotherapy. Hum Vaccin Immunother. 2014;10(11):3153–64. doi:10.4161/21645515.2014.980686.
    Article PubMed Google Scholar
  38. Saade F, Petrovsky N. Technologies for enhanced efficacy of DNA vaccines. Expert Rev Vaccines. 2012;11(2):189–209. doi:10.1586/erv.11.188.
    Article CAS PubMed PubMed Central Google Scholar
  39. Li L, Herndon JM, Truscott SM, Hansen TH, Fleming TP, Goedegebuure P, Gillanders WE. Engineering superior DNA vaccines: MHC class I single chain trimers bypass antigen processing and enhance the immune response to low affinity antigens. Vaccine. 2010;28(8):1911–8. doi:10.1016/j.vaccine.2009.10.096.
    Article CAS PubMed PubMed Central Google Scholar
  40. Norell H, Poschke I, Charo J, Wei WZ, Erskine C, Piechocki MP, Knutson KL, Bergh J, Lidbrink E, Kiessling R. Vaccination with a plasmid DNA encoding HER-2/neu together with low doses of GM-CSF and IL-2 in patients with metastatic breast carcinoma: a pilot clinical trial. J Transl Med. 2010;8:53. doi:10.1186/1479-5876-8-53.
    Article PubMed PubMed Central Google Scholar
  41. Tiriveedhi V, Fleming TP, Goedegebuure PS, Naughton M, Ma C, Lockhart C, Gao F, Gillanders WE, Mohanakumar T. Mammaglobin-A cDNA vaccination of breast cancer patients induces antigen-specific cytotoxic CD4 + ICOShi T cells. Breast Cancer Res Treat. 2013;138(1):109–18. doi:10.1007/s10549-012-2110-9.
    Article CAS PubMed Google Scholar
  42. Kang TH, Mao CP, La V, Chen A, Hung CF, Wu TC. Innovative DNA vaccine to break immune tolerance against tumor self-antigen. Hum Gene Ther. 2013;24(2):181–8. doi:10.1089/hum.2012.141.
    Article CAS PubMed Google Scholar
  43. Palucka K, Banchereau J. Cancer immunotherapy via dendritic cells. Nat Rev Cancer. 2012;12(4):265–77. doi:10.1038/nrc3258.
    Article CAS PubMed PubMed Central Google Scholar
  44. • Datta J, Terhune JH, Lowenfeld L, Cintolo JA, Xu S, Roses RE, Czerniecki BJ. Optimizing dendritic cell-based approaches for cancer immunotherapy. Yale J Biol Med 87. 2014;87(4):491–18. An important immunotherapeutic focus is on tumor associated antigens, and this paper carefully outlines the importance of dendritic cells for presentation of of tumor associated antigens and their use in immuotherapy.
  45. Koski GK, Koldovsky U, Xu S, Mick R, Sharma A, Fitzpatrick E, Weinstein S, Nisenbaum H, Levine BL, Fox K, Zhang P, Czerniecki BJ. A novel dendritic cell-based immunization approach for the induction of durable Th1-polarized anti-HER-2/neu responses in women with early breast cancer. J Immunother. 2012;35(1):54–65. doi:10.1097/CJI.0b013e318235f512.
    Article CAS PubMed PubMed Central Google Scholar
  46. Sharma A, Koldovsky U, Xu S, Mick R, Roses R, Fitzpatrick E, Weinstein S, Nisenbaum H, Levine BL, Fox K, Zhang P, Koski G, Czerniecki BJ. HER-2 pulsed dendritic cell vaccine can eliminate HER-2 expression and impact ductal carcinoma in situ. Cancer. 2012;118(17):4354–62. doi:10.1002/cncr.26734.
    Article CAS PubMed PubMed Central Google Scholar
  47. Lowenfeld L, Mick R, Datta J, Xu S, Fitzpatrick E, Fisher CS, Fox KR, DeMichele A, Zhang PJ, Weinstein SP, Roses RE, Czerniecki BJ. Dendritic Cell Vaccination Enhances Immune Responses and Induces Regression of HER2pos DCIS Independent of Route: Results of Randomized Selection Design Trial. Clin Cancer Res. 2016;. doi:10.1158/1078-0432.CCR-16-1924.
    PubMed Google Scholar
  48. De La Cruz LM, Nocera NF, Czerniecki BJ. Restoring anti-oncodriver Th1 responses with dendritic cell vaccines in HER2/neu-positive breast cancer: progress and potential. Immunotherapy. 2016;8(10):1219–32. doi:10.2217/imt-2016-0052.
    Article Google Scholar
  49. Nishimura H, Nose M, Hiai H, Minato N, Honjo T. Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity. 1999;11(2):141–51.
    Article CAS PubMed Google Scholar
  50. Stephen TL, Payne KK, Chaurio RA, Allegrezza MJ, Zhu H, Perez-Sanz J, Perales-Puchalt A, Nguyen JM, Vara-Ailor AE, Eruslanov EB, Borowsky ME, Zhang R, Laufer TM, Conejo-Garcia JR. SATB1 Expression Governs Epigenetic Repression of PD-1 in Tumor-Reactive T Cells. Immunity. 2017;46(1):51–64. doi:10.1016/j.immuni.2016.12.015.
    Article CAS PubMed Google Scholar
  51. Spranger S, Bao R, Gajewski T. Melanoma-intrinsic β-catenin signaling prevents T cell infiltration and anti-tumor immunity. J immunother cancer. 2014;2(3):O15.
    Article PubMed Central Google Scholar
  52. Nanda R, Chow LQ, Dees EC, Berger R, Gupta S, Geva R, Pusztai L, Pathiraja K, Aktan G, Cheng JD, Karantza V, Buisseret L. Pembrolizumab in Patients With Advanced Triple-Negative Breast Cancer: Phase Ib KEYNOTE-012 Study. J Clin Oncol. 2016;34(21):2460–7. doi:10.1200/JCO.2015.64.8931.
    Article CAS PubMed Google Scholar
  53. Emens LA, Braiteh FS, Cassier P, Delord J-P, Eder JP, Fasso M, Xiao Y, Wang Y, Molinero L, Chen DS. Inhibition of PD-L1 by MPDL3280A leads to clinical activity in patients with metastatic triple-negative breast cancer (TNBC). 2015;2859.
  54. Adams S, Diamond J, Hamilton E, Pohlmann P, Tolaney S, Molinero L. Phase Ib trial of atezolizumab in combination with nab-paclitaxel in patients with metastatic triple-negative breast cancer (mTNBC). J Clin Oncol. 2016;34(suppl: abstr):1009.
    Google Scholar
  55. Rugo H, Delord J, Im S, Ott P, Piha-Paul S, Bedard P, Sachdev J, Le Tourneau C, Van Brummelen E, Varga A. Abstract S5-07: 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. AACR,.2016
  56. Sharma P, Allison JP. Immune checkpoint targeting in cancer therapy: toward combination strategies with curative potential. Cell. 2015;161(2):205–14.
    Article CAS PubMed Google Scholar
  57. Voutsadakis IA. Immune Blockade Inhibition in Breast Cancer. Anticancer Res. 2016;36(11):5607–22. doi:10.21873/anticanres.11145.
    Article PubMed Google Scholar
  58. Guerriero JL, Sotayo A, Ponichtera HE, Castrillon JA, Pourzia AL, Schad S, Johnson SF, Carrasco RD, Lazo S, Bronson RT, Davis SP, Lobera M, Nolan MA, Letai A. Class IIa HDAC inhibition reduces breast tumours and metastases through anti-tumour macrophages. Nature. 2017;543(7645):428–32. doi:10.1038/nature21409.
    Article CAS PubMed Google Scholar
  59. Schmittnaegel M, Rigamonti N, Kadioglu E, Cassara A, Wyser Rmili C, Kiialainen A, Kienast Y, Mueller HJ, Ooi CH, Laoui D, De Palma M. Dual angiopoietin-2 and VEGFA inhibition elicits antitumor immunity that is enhanced by PD-1 checkpoint blockade. Sci Transl Med. 2017;. doi:10.1126/scitranslmed.aak9670.
    PubMed Google Scholar
  60. Schalper KA, Velcheti V, Carvajal D, Wimberly H, Brown J, Pusztai L, Rimm DL. In situ tumor PD-L1 mRNA expression is associated with increased TILs and better outcome in breast carcinomas. Clin Cancer Res. 2014;20(10):2773–82.
    Article CAS PubMed Google Scholar
  61. Cimino-Mathews A, Thompson E, Taube JM, Ye X, Lu Y, Meeker A, Xu H, Sharma R, Lecksell K, Cornish TC, Cuka N, Argani P, Emens LA. PD-L1 (B7-H1) expression and the immune tumor microenvironment in primary and metastatic breast carcinomas. Hum Pathol. 2016;47(1):52–63. doi:10.1016/j.humpath.2015.09.003.
    Article CAS PubMed Google Scholar
  62. Ghebeh H, Mohammed S, Al-Omair A, Qattan A, Lehe C, Al-Qudaihi G, Elkum N, Alshabanah M, Bin Amer S, Tulbah A, Ajarim D, Al-Tweigeri T, Dermime S. The B7-H1 (PD-L1) T lymphocyte-inhibitory molecule is expressed in breast cancer patients with infiltrating ductal carcinoma: correlation with important high-risk prognostic factors. Neoplasia. 2006;8(3):190–8. doi:10.1593/neo.05733.
    Article CAS PubMed PubMed Central Google Scholar
  63. Sun WY, Lee YK, Koo JS. Expression of PD-L1 in triple-negative breast cancer based on different immunohistochemical antibodies. J Transl Med. 2016;14(1):173. doi:10.1186/s12967-016-0925-6.
    Article PubMed PubMed Central Google Scholar
  64. Brignone C, Gutierrez M, Mefti F, Brain E, Jarcau R, Cvitkovic F, Bousetta N, Medioni J, Gligorov J, Grygar C, Marcu M, Triebel F. 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. doi:10.1186/1479-5876-8-71.
    Article PubMed PubMed Central Google Scholar
  65. Wong HH, Lemoine NR, Wang Y. Oncolytic Viruses for Cancer Therapy: Overcoming the Obstacles. Viruses. 2010;2(1):78–106. doi:10.3390/v2010078.
    Article CAS PubMed PubMed Central Google Scholar
  66. Fukuhara H, Ino Y, Todo T. Oncolytic virus therapy: A new era of cancer treatment at dawn. Cancer Sci. 2016;107(10):1373–9. doi:10.1111/cas.13027.
    Article CAS PubMed PubMed Central Google Scholar
  67. Conner J, Braidwood L. Expression of inhibitor of growth 4 by HSV1716 improves oncolytic potency and enhances efficacy. Cancer Gene Ther. 2012;19(7):499–507. doi:10.1038/cgt.2012.24.
    Article CAS PubMed Google Scholar
  68. Seth P, Wang Z-G, Pister A, Zafar MB, Kim S, Guise T, Wakefield L. Development of oncolytic adenovirus armed with a fusion of soluble transforming growth factor-β receptor II and human immunoglobulin Fc for breast cancer therapy. Hum Gene Ther. 2006;17(11):1152–61.
    Article CAS PubMed Google Scholar
  69. Posey AD Jr, Schwab RD, Boesteanu AC, Steentoft C, Mandel U, Engels B, Stone JD, Madsen TD, Schreiber K, Haines KM, Cogdill AP, Chen TJ, Song D, Scholler J, Kranz DM, Feldman MD, Young R, Keith B, Schreiber H, Clausen H, Johnson LA, June CH. Engineered CAR T Cells Targeting the Cancer-Associated Tn-Glycoform of the Membrane Mucin MUC1 Control Adenocarcinoma. Immunity. 2016;44(6):1444–54. doi:10.1016/j.immuni.2016.05.014.
    Article CAS PubMed PubMed Central Google Scholar
  70. Whilding LM, Parente-Pereira AC, Zabinski T, Davies DM, Petrovic RMG, Kao YV, Saxena SA, Romain A, Costa-Guerra JA, Violette S, Itamochi H, Ghaem-Maghami S, Vallath S, Marshall JF, Maher J. Targeting of Aberrant alphavbeta6 Integrin Expression in Solid Tumors Using Chimeric Antigen Receptor-Engineered T Cells. Mol Ther. 2017;25(1):259–73. doi:10.1016/j.ymthe.2016.10.012.
    Article CAS PubMed Google Scholar
  71. Vogel CL, Cobleigh MA, Tripathy D, Gutheil JC, Harris LN, Fehrenbacher L, Slamon DJ, Murphy M, Novotny WF, Burchmore M, Shak S, Stewart SJ, Press M. Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol. 2002;20(3):719–26. doi:10.1200/JCO.2002.20.3.719.
    Article CAS PubMed Google Scholar
  72. 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(34):5838–47. doi:10.1200/JCO.2009.22.1507.
    Article CAS PubMed Google Scholar
  73. Hudis CA. Trastuzumab–mechanism of action and use in clinical practice. N Engl J Med. 2007;357(1):39–51. doi:10.1056/NEJMra043186.
    Article CAS PubMed Google Scholar
  74. 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(7):2343–6.
    Article CAS PubMed Google Scholar
  75. Gianni L, Pienkowski T, Im YH, Roman L, Tseng LM, Liu MC, Lluch A, Staroslawska E, de la Haba-Rodriguez J, Im SA, Pedrini JL, Poirier B, Morandi P, Semiglazov V, Srimuninnimit V, Bianchi G, Szado T, Ratnayake J, Ross G, Valagussa P. 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(1):25–32. doi:10.1016/S1470-2045(11)70336-9.
    Article CAS PubMed Google Scholar
  76. Bang YJ, Giaccone G, Im SA, Oh DY, Bauer TM, Nordstrom JL, Li H, Chichili GR, Moore PA, Hong S, Stewart SJ, Baughman JE, Lechleider RJ, Burris HA. First-in-human phase 1 study of margetuximab (MGAH22), an Fc-modified chimeric monoclonal antibody, in patients with HER2-positive advanced solid tumors. Ann Oncol. 2017;28(4):855–61. doi:10.1093/annonc/mdx002.
    CAS PubMed Google Scholar
  77. Dasgupta S, Kumar V. Type II NKT cells: a distinct CD1d-restricted immune regulatory NKT cell subset. Immunogenetics. 2016;68(8):665–76. doi:10.1007/s00251-016-0930-1.
    Article CAS PubMed Google Scholar
  78. Rutkowski MR, Stephen TL, Svoronos N, Allegrezza MJ, Tesone AJ, Perales-Puchalt A, Brencicova E, Escovar-Fadul X, Nguyen JM, Cadungog MG, Zhang R, Salatino M, Tchou J, Rabinovich GA, Conejo-Garcia JR. Microbially driven TLR5-dependent signaling governs distal malignant progression through tumor-promoting inflammation. Cancer Cell. 2015;27(1):27–40. doi:10.1016/j.ccell.2014.11.009.
    Article CAS PubMed Google Scholar
  79. Payne KK. Lymphocyte-mediated Immune Regulation in Health and Disease: The Treg and gammadelta T Cell Co-conspiracy. Immunol Invest. 2016;45(8):767–75. doi:10.1080/08820139.2016.1213278.
    Article CAS PubMed Google Scholar
  80. Gobert M, Treilleux I, Bendriss-Vermare N, Bachelot T, Goddard-Leon S, Arfi V, Biota C, Doffin AC, Durand I, Olive D, Perez S, Pasqual N, Faure C, Ray-Coquard I, Puisieux A, Caux C, Blay JY, Menetrier-Caux C. 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(5):2000–9. doi:10.1158/0008-5472.CAN-08-2360.
    Article CAS PubMed Google Scholar
  81. Yan M, Jene N, Byrne D, Millar EK, O’Toole SA, McNeil CM, Bates GJ, Harris AL, Banham AH, Sutherland RL, Fox SB. Recruitment of regulatory T cells is correlated with hypoxia-induced CXCR4 expression, and is associated with poor prognosis in basal-like breast cancers. Breast Cancer Res. 2011;13(2):R47. doi:10.1186/bcr2869.
    Article CAS PubMed PubMed Central Google Scholar
  82. Mougiakakos D, Choudhury A, Lladser A, Kiessling R, Johansson CC. Regulatory T cells in cancer. Adv Cancer Res. 2010;107:57–117. doi:10.1016/S0065-230X(10)07003-X.
    Article CAS PubMed Google Scholar
  83. Schmidt A, Oberle N, Krammer PH. Molecular mechanisms of treg-mediated T cell suppression. Front Immunol. 2012;3:51. doi:10.3389/fimmu.2012.00051.
    CAS PubMed PubMed Central Google Scholar
  84. Fisher SA, Aston WJ, Chee J, Khong A, Cleaver AL, Solin JN, Ma S, Lesterhuis WJ, Dick I, Holt RA, Creaney J, Boon L, Robinson B, Lake RA. Transient Treg depletion enhances therapeutic anti-cancer vaccination. Immun Inflamm Dis. 2017;5(1):16–28. doi:10.1002/iid3.136.
    Article CAS PubMed Google Scholar
  85. Rech AJ, Mick R, Martin S, Recio A, Aqui NA, Powell DJ Jr, Colligon TA, Trosko JA, Leinbach LI, Pletcher CH, Tweed CK, DeMichele A, Fox KR, Domchek SM, Riley JL, Vonderheide RH. CD25 blockade depletes and selectively reprograms regulatory T cells in concert with immunotherapy in cancer patients. Sci Transl Med. 2012;4(134):134ra162. doi:10.1126/scitranslmed.3003330.
    Article Google Scholar
  86. Rech AJ, Vonderheide RH. Clinical use of anti-CD25 antibody daclizumab to enhance immune responses to tumor antigen vaccination by targeting regulatory T cells. Ann N Y Acad Sci. 2009;1174:99–106. doi:10.1111/j.1749-6632.2009.04939.x.
    Article CAS PubMed Google Scholar
  87. Franklin RA, Liao W, Sarkar A, Kim MV, Bivona MR, Liu K, Pamer EG, Li MO. The cellular and molecular origin of tumor-associated macrophages. Science. 2014;344(6186):921–5. doi:10.1126/science.1252510.
    Article CAS PubMed PubMed Central Google Scholar
  88. • Mantovani A, Marchesi F, Malesci A, Laghi L, Allavena P. Tumour-associated macrophages as treatment targets in oncology. Nat Rev Clin Oncol. 2016;doi:10.1038/nrclinonc.2016.217. Macrophages have become a recent focus in understanding the tumor microenvironment, and this paper discusses the dual pro- and anti-inflammatory behavior exhibited by macrophages and the ultimate impact on tumor progression and response to therapy.
  89. Martinez FO, Gordon S (2014) The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime Rep 6:13. doi:10.12703/P6–13.
  90. Biswas SK, Mantovani A. Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat Immunol. 2010;11(10):889–96. doi:10.1038/ni.1937.
    Article CAS PubMed Google Scholar
  91. 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(11):549–55.
    Article CAS PubMed Google Scholar
  92. Bronte V, Brandau S, Chen SH, Colombo MP, Frey AB, Greten TF, Mandruzzato S, Murray PJ, Ochoa A, Ostrand-Rosenberg S, Rodriguez PC, Sica A, Umansky V, Vonderheide RH, Gabrilovich DI. Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards. Nat Commun. 2016;7:12150. doi:10.1038/ncomms12150.
    Article CAS PubMed PubMed Central Google Scholar
  93. De Palma M, Lewis CE. Macrophage regulation of tumor responses to anticancer therapies. Cancer Cell. 2013;23(3):277–86. doi:10.1016/j.ccr.2013.02.013.
    Article PubMed Google Scholar
  94. DeNardo DG, Brennan DJ, Rexhepaj E, Ruffell B, Shiao SL, Madden SF, Gallagher WM, Wadhwani N, Keil SD, Junaid SA, Rugo HS, Hwang ES, Jirstrom K, West BL, Coussens LM. Leukocyte complexity predicts breast cancer survival and functionally regulates response to chemotherapy. Cancer Discov. 2011;1(1):54–67. doi:10.1158/2159-8274.CD-10-0028.
    Article CAS PubMed PubMed Central Google Scholar

Download references