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Review

Immunotherapy for the treatment of breast cancer

ORCID Icon, ORCID Icon, ORCID Icon, ORCID Icon, ORCID Icon, ORCID Icon & ORCID Icon show all
Pages 797-812 | Received 01 Nov 2016, Accepted 25 Apr 2017, Published online: 08 May 2017

References

  • Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015; 136(5):E359–86. PubMed PMID: 25220842. 10.1002/ijc.29210
  • Tao JJ, Visvanathan K, Wolff AC. Long term side effects of adjuvant chemotherapy in patients with early breast cancer. Breast. 2015;24(Suppl 2):S149–53. PubMed PMID: 26299406; PubMed Central PMCID: PMC4743500. 10.1016/j.breast.2015.07.035
  • Kayl AE, Meyers CA. Side-effects of chemotherapy and quality of life in ovarian and breast cancer patients. Curr Opin Obstet Gynecol. 2006;18(1):24–28. PubMed PMID: 16493256. 10.1097/01.gco.0000192996.20040.24
  • Hunt N, McHale S. The psychological impact of alopecia. Bmj. 2005;331(7522):951–953. PubMed PMID: 16239692; PubMed Central PMCID: PMC1261195. 10.1136/bmj.331.7522.951
  • Couzin-Frankel J. Breakthrough of the year 2013. Cancer Immunotherapy. Science. 2013;342(6165):1432–1433. PubMed PMID: 24357284. 10.1126/science.342.6165.1432.
  • Dushyanthen S, Beavis PA, Savas P, et al. Relevance of tumor-infiltrating lymphocytes in breast cancer. BMC Med. 2015;13:202. PubMed PMID: 26300242; PubMed Central PMCID: PMC4547422. DOI:10.1186/s12916-015-0431-3
  • Martinet L, Garrido I, Filleron T, et al. Human solid tumors contain high endothelial venules: association with T- and B-lymphocyte infiltration and favorable prognosis in breast cancer. Cancer Res. 2011; 71(17):5678–5687. PubMed PMID: 21846823. 10.1158/0008-5472.CAN-11-0431
  • Mao Y, Qu Q, Zhang Y, et al. The value of tumor infiltrating lymphocytes (TILs) for predicting response to neoadjuvant chemotherapy in breast cancer: a systematic review and meta-analysis. Plos One. 2014;9(12):e115103. PubMed PMID: 25501357; PubMed Central PMCID: PMC4264870. 10.1371/journal.pone.0115103.
  • Garcia-Teijido P, Cabal ML, Fernandez IP, et al. Tumor-infiltrating lymphocytes in triple negative breast cancer: the future of immune targeting. Clin Med Insights Oncol. 2016;10(Suppl 1):31–39. PubMed PMID: 27081325; PubMed Central PMCID: PMC4822722. 10.4137/CMO.S34540
  • Disis ML, Stanton SE. Triple-negative breast cancer: immune modulation as the new treatment paradigm. Am Soc Clin Oncol Educational Book /ASCO Am Soc Clin Oncol Meet. 2015:e25–30. PubMed PMID: 25993181. DOI:10.14694/EdBook_AM.2015.35.e25
  • Soliman H, Immunotherapy strategies in the treatment of breast cancer. Cancer Control. 2013;20(1):17–21. PubMed PMID: 23302903
  • Gabrilovich D, Pisarev V, Tumor escape from immune response: mechanisms and targets of activity. Curr Drug Targets. 2003;4(7):525–536. PubMed PMID: 14535653
  • Van Baren N, Van Den Eynde BJ. Tryptophan-degrading enzymes in tumoral immune resistance. Front Immunol. 2015;6:34. PubMed PMID: 25691885; PubMed Central PMCID: PMC4315104. DOI:10.3389/fimmu.2015.00034
  • Soliman H, Rawal B, Fulp J, et al. Analysis of indoleamine 2-3 dioxygenase (IDO1) expression in breast cancer tissue by immunohistochemistry. Cancer Immunol Immunother. 2013; 62(5):829–837. PubMed PMID: 23344392; PubMed Central PMCID: PMC4501769. 10.1007/s00262-013-1393-y
  • Curti A, Trabanelli S, Salvestrini V, et al. The role of indoleamine 2,3-dioxygenase in the induction of immune tolerance: focus on hematology. Blood. 2009;113(11):2394–2401. PubMed PMID: 19023117. 10.1182/blood-2008-07-144485
  • Chen JY, Li CF, Kuo CC, et al. Cancer/stroma interplay via cyclooxygenase-2 and indoleamine 2,3-dioxygenase promotes breast cancer progression. Breast Cancer Res. 2014;16(4):410. PubMed PMID: 25060643; PubMed Central PMCID: PMC4220086. 10.1186/s13058-014-0410-1
  • Duchnowska R, Peksa R, Radecka 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;18(1):43. PubMed PMID: 27117582; PubMed Central PMCID: PMC4847231. DOI:10.1186/s13058-016-0702-8.
  • Yu H, Yang J, Jiao S, et al. Cytotoxic T lymphocyte antigen 4 expression in human breast cancer: implications for prognosis. Cancer Immunol Immunother. 2015;64(7):853–860. PubMed PMID: 25893809; PubMed Central PMCID: PMC4481300. 10.1007/s00262-015-1696-2
  • Sabatier R, Finetti P, Mamessier E, et al. Prognostic and predictive value of PDL1 expression in breast cancer. Oncotarget. 2015; 6(7):5449–5464. PubMed PMID: 25669979; PubMed Central PMCID: PMC4467160. 10.18632/oncotarget.3216
  • Li Z, Dong P, Ren M, et al. PD-L1 expression is associated with tumor FOXP3(+) regulatory T-cell infiltration of breast cancer and poor prognosis of patient. J Cancer. 2016; 7(7):784–793. PubMed PMID: 27162536; PubMed Central PMCID: PMC4860794. 10.7150/jca.14549
  • Oleinika K, Nibbs RJ, Graham GJ, et al. Suppression, subversion and escape: the role of regulatory T cells in cancer progression. Clin Exp Immunol. 2013;171(1):36–45. PubMed PMID: 23199321; PubMed Central PMCID: PMC3530093. 10.1111/j.1365-2249.2012.04657.x
  • Nishikawa H, Sakaguchi S. Regulatory T cells in cancer immunotherapy. Curr Opin Immunol. 2014;27:1–7. PubMed PMID: 24413387. DOI:10.1016/j.coi.2013.12.005.
  • Shou J, Zhang Z, Lai Y, et al. Worse outcome in breast cancer with higher tumor-infiltrating FOXP3+ Tregs: a systematic review and meta-analysis. BMC Cancer. 2016;16:687. PubMed PMID: 27566250; PubMed Central PMCID: PMC5002190. DOI:10.1186/s12885-016-2732-0
  • Sansom DM. CD28, CTLA-4 and their ligands: who does what and to whom? Immunology. 2000;101(2):169–177. Epub 2000/09/30. PubMed PMID: 11012769; PubMed Central PMCID: PMC2327073.
  • Yu H, Yang J, Jiao S, et al. Cytotoxic T lymphocyte antigen 4 expression in human breast cancer: implications for prognosis. Cancer Immunol Immunother. 2015; 64(7): 853–860. Epub 2015/04/22. PubMed PMID: 25893809; PubMed Central PMCID: PMC4481300. 10.1007/s00262-015-1696-2
  • Contardi E, Palmisano GL, Tazzari PL, et al. CTLA-4 is constitutively expressed on tumor cells and can trigger apoptosis upon ligand interaction. Int J Cancer. 2005; 117(4): 538–550. Epub 2005/05/25. PubMed PMID: 15912538. 10.1002/ijc.21155
  • Jaberipour M, Habibagahi M, Hosseini A, et al. Increased CTLA-4 and FOXP3 transcripts in peripheral blood mononuclear cells of patients with breast cancer. Pathol Oncol Res. 2010; 16(4): 547–551. Epub 2010/03/23. PubMed PMID: 20306312. 10.1007/s12253-010-9256-8
  • Erfani N, Razmkhah M, Ghaderi A. Circulating soluble CTLA4 (sCTLA4) is elevated in patients with breast cancer. Cancer Invest. 2010; 28(8): 828–832. Epub 2010/05/21. PubMed PMID: 20482250. 10.3109/07357901003630934
  • Mao H, Zhang L, Yang Y, et al. New insights of CTLA-4 into its biological function in breast cancer. Curr Cancer Drug Targets. 2010;10(7):728–736. Epub 2010/06/29. PubMed PMID: 20578982.
  • Shimomura A, Fujiwara Y, Kondo S, et al. Tremelimumab-associated tumor regression following after initial progression: two case reports. Immunotherapy. 2016; 8(1):9–15. PubMed PMID: 26427600. 10.2217/imt.15.89
  • Bertrand A, Kostine M, Barnetche T, et al. Immune related adverse events associated with anti-CTLA-4 antibodies: systematic review and meta-analysis. BMC Med. 2015;13:211. PubMed PMID: 26337719; PubMed Central PMCID: PMC4559965. DOI:10.1186/s12916-015-0455-8
  • Fransen MF, Van Der Sluis TC, Ossendorp F, et al. Controlled local delivery of CTLA-4 blocking antibody induces CD8+ T-cell-dependent tumor eradication and decreases risk of toxic side effects. Clin Cancer Res. 2013;19(19):5381–5389. PubMed PMID: 23788581. 10.1158/1078-0432.CCR-12-0781
  • Intlekofer AM, Thompson CB. At the bench: preclinical rationale for CTLA-4 and PD-1 blockade as cancer immunotherapy. J Leukoc Biol. 2013;94(1):25–39. PubMed PMID: 23625198; PubMed Central PMCID: PMC3685017. 10.1189/jlb.1212621
  • Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012; 12(4): 252–264. Epub 2012/03/23. PubMed PMID: 22437870; PubMed Central PMCID: PMC4856023. 10.1038/nrc3239
  • Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012; 366(26): 2443–2454. Epub 2012/06/05. PubMed PMID: 22658127; PubMed Central PMCID: PMC3544539. 10.1056/NEJMoa1200690
  • Muenst S, Soysal SD, Gao F, et al. 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): 667–676. Epub 2013/06/13. PubMed PMID: 23756627; PubMed Central PMCID: PMC3885332. 10.1007/s10549-013-2581-3
  • 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. Epub 2016/06/12. PubMed PMID: 27286842; PubMed Central PMCID: PMC4902914. 10.1186/s12967-016-0925-6
  • 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(1): 15–24. Epub 2014/05/21. PubMed PMID: 24842267; PubMed Central PMCID: PMC4180714. 10.1007/s10549-014-2988-5
  • Mazel M, Jacot W, Pantel K, et al. Frequent expression of PD-L1 on circulating breast cancer cells. Mol Oncol. 2015; 9(9): 1773–1782. Epub 2015/06/22. PubMed PMID: 26093818. 10.1016/j.molonc.2015.05.009
  • Nanda R, Chow LQ, Dees EC, et al. Pembrolizumab in patients with advanced triple-negative breast cancer: phase Ib KEYNOTE-012 study. J Clin Oncol. 2016; 34(21):2460–2467. PubMed PMID: 27138582. 10.1200/JCO.2015.64.8931
  • Rugo HS, Delord J-P, Im SA, 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. 8–12. AACR San Antonio. Philadelphia, TX 2015 S5-07;2015.
  • Adams SRDJ, Hamilton E, Raffin Pohlmann P, et al. Phase Ib trial of atezolizumab in combination with nab-paclitaxel in patients with metastatic triple-negative breast cancer (mTNBC) ASCO annual meeting; Chicago, Illinois. J Clin Oncol. 2016;34:abstr1009.
  • Dirix LY, Takacs I, Nikolinakos P, et al. 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 Cancer Symposium; San Antonio, TX 2015 S1-07.
  • Gallois A, Silva I, Osman I, et al. Reversal of natural killer cell exhaustion by TIM-3 blockade. Oncoimmunology. 2014;3(12):e946365. PubMed PMID: 25964857; PubMed Central PMCID: PMC4353130. 10.4161/21624011.2014.946365
  • Zhu S, Lin J, Qiao G, et al. Tim-3 identifies exhausted follicular helper T cells in breast cancer patients. Immunobiology. 2016;221(9):986–993. PubMed PMID: 27156907. 10.1016/j.imbio.2016.04.005
  • Sakuishi K, Apetoh L, Sullivan JM, et al. Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity. J Exp Med. 2010;207(10):2187–2194. PubMed PMID: 20819927; PubMed Central PMCID: PMC2947065. 10.1084/jem.20100643
  • Chiba S, Baghdadi M, Akiba H, et al. Tumor-infiltrating DCs suppress nucleic acid-mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1. Nat Immunol. 2012; 13(9):832–842. PubMed PMID: 22842346; PubMed Central PMCID: PMC3622453. 10.1038/ni.2376
  • Nguyen LT, Ohashi PS. Clinical blockade of PD1 and LAG3–potential mechanisms of action. Nat Reviews Immunol. 2015;15(1):45–56. PubMed PMID: 25534622. 10.1038/nri3790
  • Grosso JF, Kelleher CC, Harris TJ, et al. LAG-3 regulates CD8+ T cell accumulation and effector function in murine self- and tumor-tolerance systems. J Clin Invest. 2007; 117(11): 3383–3392. Epub 2007/10/13. PubMed PMID: 17932562; PubMed Central PMCID: PMC2000807. 10.1172/JCI31184
  • Woo SR, Turnis ME, Goldberg MV, et al. Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T-cell function to promote tumoral immune escape. Cancer Res. 2012; 72(4): 917–927. Epub 2011/12/22. PubMed PMID: 22186141; PubMed Central PMCID: PMC3288154. 10.1158/0008-5472.CAN-11-1620
  • Bottai G, Raschioni C, Losurdo A, et al. An immune stratification reveals a subset of PD-1/LAG-3 double-positive triple-negative breast cancers. Breast Cancer Res. 2016; 18(1):121. PubMed PMID: 27912781; PubMed Central PMCID: PMC5135782. 10.1186/s13058-016-0783-4
  • Triebel F, Hacene K, Pichon MF. A soluble lymphocyte activation gene-3 (sLAG-3) protein as a prognostic factor in human breast cancer expressing estrogen or progesterone receptors. Cancer Lett. 2006;235(1):147–153. PubMed PMID: 15946792. 10.1016/j.canlet.2005.04.015
  • Fougeray S, Brignone C, Triebel F. A soluble LAG-3 protein as an immunopotentiator for therapeutic vaccines: preclinical evaluation of IMP321. Vaccine. 2006; 24(26): 5426–5433. Epub 2006/04/20. PubMed PMID: 16621192. 10.1016/j.vaccine.2006.03.050
  • 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. Epub 2010/07/27. PubMed PMID: 20653948; PubMed Central PMCID: PMC2920252. 10.1186/1479-5876-8-71
  • Clifton GT, Peoples GE. Overcoming cancer immune tolerance and escape. Clin Cancer Res. 2009;15(3):749–751. PubMed PMID: 19188142. 10.1158/1078-0432.CCR-08-2805
  • Moran AE, Kovacsovics-Bankowski M, Weinberg AD. The TNFRs OX40, 4-1BB, and CD40 as targets for cancer immunotherapy. Curr Opin Immunol. 2013;25(2):230–237. PubMed PMID: 23414607; PubMed Central PMCID: PMC3815601. 10.1016/j.coi.2013.01.004
  • Piconese S, Valzasina B, Colombo MP. OX40 triggering blocks suppression by regulatory T cells and facilitates tumor rejection. J Exp Med. 2008;205(4):825–839. PubMed PMID: 18362171; PubMed Central PMCID: PMC2292222. 10.1084/jem.20071341
  • Weinberg AD, Morris NP, Kovacsovics-Bankowski M, et al. Science gone translational: the OX40 agonist story. Immunol Rev. 2011; 244(1): 218–231. Epub 2011/10/25. PubMed PMID: 22017441; PubMed Central PMCID: PMC3622727. 10.1111/j.1600-065X.2011.01069.x
  • Linch SN, McNamara MJ, Redmond WL. OX40 Agonists and combination immunotherapy: putting the pedal to the metal. Front Oncol. 2015;5:34. PubMed PMID: 25763356; PubMed Central PMCID: PMC4329814. DOI:10.3389/fonc.2015.00034
  • Powderly JDGM, Wang D, Chae YW, et al. A phase 1b/2, open-label study to evaluate the safety and tolerability of MEDI6469 in combination with immune therapeutic agents or therapeutic mAbs in patients with selected advanced solid tumors or aggressive B-cell lymphomas. ASCO: J Clin Oncol. 2015;33:TPS3091.
  • Infante JRHA, Pishvaian MJ, Quan Man Chow L, et al. A phase Ib dose escalation study of the OX40 agonist MOXR0916 and the PD-L1 inhibitor atezolizumab in patients with advanced solid tumors. ASCO: J Clin Oncol. 2016;34:abstr 101.
  • Palucka K, Banchereau J. Dendritic-cell-based therapeutic cancer vaccines. Immunity. 2013;39(1):38–48. PubMed PMID: 23890062; PubMed Central PMCID: PMC3788678. 10.1016/j.immuni.2013.07.004
  • Sharma P, Allison JP. Immune checkpoint targeting in cancer therapy: toward combination strategies with curative potential. Cell. 2015;161(2):205–214. PubMed PMID: 25860605. 10.1016/j.cell.2015.03.030
  • 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. PubMed PMID: 24790732; PubMed Central PMCID: PMC3991156. 10.1177/2051013614525375
  • Bentzen AK, Marquard AM, Lyngaa R, et al. Large-scale detection of antigen-specific T cells using peptide-MHC-I multimers labeled with DNA barcodes. Nat Biotechnol. 2016; 34(10):1037–1045. PubMed PMID: 27571370. 10.1038/nbt.3662
  • Zhang Z, Wang J, Tacha DE, et al. Folate receptor alpha associated with triple-negative breast cancer and poor prognosis. Arch Pathol Lab Med. 2014; 138(7):890–895. PubMed PMID: 24028341. 10.5858/arpa.2013-0309-OA
  • Laubreton D, Bay S, Sedlik C, et al. The fully synthetic MAG-Tn3 therapeutic vaccine containing the tetanus toxoid-derived TT830-844 universal epitope provides anti-tumor immunity. Cancer Immunol Immunother. 2016; 65(3):315–325. PubMed PMID: 26847142; PubMed Central PMCID: PMC4779142. 10.1007/s00262-016-1802-0
  • Zhu X, Verma S. Targeted therapy in her2-positive metastatic breast cancer: a review of the literature. Curr Oncology. 2015;22(Suppl 1):S19–28. PubMed PMID: 25848336; PubMed Central PMCID: PMC4381788. 10.3747/co.22.2363
  • Schneble EJ, Perez SA, Murray JL, et al. Abstract 134. Primary analysis of the prospective, randomized, phase II trial of GP2+GM–CSF vaccine versus GM–CSF alone administered in the adjuvant setting to high-risk breast cancer patients. Breast Cancer Symposium: J Clin Oncol. 2014;26:abstr134.
  • Schneble EJ, Berry JS, Trappey FA, et al. The HER2 peptide nelipepimut-S (E75) vaccine (NeuVax) in breast cancer patients at risk for recurrence: correlation of immunologic data with clinical response. Immunotherapy. 2014; 6(5):519–531. PubMed PMID: 24896623. 10.2217/imt.14.22
  • Kametani YMA, Tsuda B, Tokuda Y, et al. Vaccination Therapy. Antibodies. 2015;4:225–230. DOI:10.3390/antib4030225
  • Kaumaya PT. A paradigm shift: cancer therapy with peptide-based B-cell epitopes and peptide immunotherapeutics targeting multiple solid tumor types: emerging concepts and validation of combination immunotherapy. Hum Vaccin Immunother. 2015;11(6):1368–1386. PubMed PMID: 25874884; PubMed Central PMCID: PMC4514180. 10.1080/21645515.2015.1026495
  • Kaumaya PT, Foy KC, Garrett J, et al. Phase I active immunotherapy with combination of two chimeric, human epidermal growth factor receptor 2, B-cell epitopes fused to a promiscuous T-cell epitope in patients with metastatic and/or recurrent solid tumors. J Clin Oncol. 2009; 27(31):5270–5277. PubMed PMID: 19752336; PubMed Central PMCID: PMC2773479. 10.1200/JCO.2009.22.3883
  • Peres Lde P, Da Luz FA, Pultz Bdos A, et al. Peptide vaccines in breast cancer: the immunological basis for clinical response. Biotechnol Adv. 2015; 33(8):1868–1877. PubMed PMID: 26523780. 10.1016/j.biotechadv.2015.10.013
  • Slingluff CL Jr. The present and future of peptide vaccines for cancer: single or multiple, long or short, alone or in combination? Cancer J. 2011;17(5):343–350. PubMed PMID: 21952285; PubMed Central PMCID: PMC3204371. 10.1097/PPO.0b013e318233e5b2
  • Von Boehmer L, Mattle M, Bode P, et al. NY-ESO-1-specific immunological pressure and escape in a patient with metastatic melanoma. Cancer Immun. 2013;13:12. PubMed PMID: 23882157; PubMed Central PMCID: PMC3718732.
  • Nicholaou T, Chen W, Davis ID, et al. Immunoediting and persistence of antigen-specific immunity in patients who have previously been vaccinated with NY-ESO-1 protein formulated in ISCOMATRIX. Cancer Immunol Immunother. 2011; 60(11):1625–1637. PubMed PMID: 21698545. 10.1007/s00262-011-1041-3
  • Madan RA, Arlen PM, Gulley JL. PANVAC-VF: poxviral-based vaccine therapy targeting CEA and MUC1 in carcinoma. Expert Opin Biol Ther. 2007;7(4):543–554. PubMed PMID: 17373905. 10.1517/14712598.7.4.543
  • Heery CR, Ibrahim NK, Arlen PM, et al. Docetaxel alone or in combination with a therapeutic cancer vaccine (PANVAC) in patients with metastatic breast cancer: a randomized clinical trial. JAMA Oncol. 2015; 1(8):1087–1095. 2736.PubMed PMID: 26291768. 10.1001/jamaoncol.2015
  • Avigan D, Vasir B, Gong J, et al. Fusion cell vaccination of patients with metastatic breast and renal cancer induces immunological and clinical responses. Clin Cancer Res. 2004; 10(14):4699–4708. PubMed PMID: 15269142. 10.1158/1078-0432.CCR-04-0347
  • Park JW, Melisko ME, Esserman LJ, et al. Treatment with autologous antigen-presenting cells activated with the HER-2 based antigen Lapuleucel-T: results of a phase I study in immunologic and clinical activity in HER-2 overexpressing breast cancer. J Clin Oncol. 2007;25(24):3680–3687. 5718.PubMed PMID: 17704416. 10.1200/JCO.2006.10
  • Benteyn D, Heirman C, Bonehill A, et al. mRNA-based dendritic cell vaccines. Expert Rev Vaccines. 2015;14(2):161–176. PubMed PMID: 25196947. 10.1586/14760584.2014.957684
  • Cheever MA, Higano CS. PROVENGE (Sipuleucel-T) in prostate cancer: the first FDA-approved therapeutic cancer vaccine. Clin Cancer Res. 2011;17(11):3520–3526. PubMed PMID: 21471425. 10.1158/1078-0432.CCR-10-3126
  • Brossart P, Wirths S, Stuhler G, et al., Induction of cytotoxic T-lymphocyte responses in vivo after vaccinations with peptide-pulsed dendritic cells. Blood. 2000;96(9):3102–3108. PubMed PMID: 11049990
  • Apostolopoulos V, Pietersz GA, Tsibanis A, et al. Dendritic cell immunotherapy: clinical outcomes. Clin Transl Immunology. 2014;3(7):e21. PubMed PMID: 25505969; PubMed Central PMCID: PMC4232065. DOI:10.1038/cti.2014.14.
  • 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(9):1485–1499. PubMed PMID: 17285289. 10.1007/s00262-007-0293-4
  • Vasir B, Wu Z, Crawford K, et al. Fusions of dendritic cells with breast carcinoma stimulate the expansion of regulatory T cells while concomitant exposure to IL-12, CpG oligodeoxynucleotides, and anti-CD3/CD28 promotes the expansion of activated tumor reactive cells. J Immunology. 2008;181(1):808–821. PubMed PMID: 18566447; PubMed Central PMCID: PMC2938172.
  • Datta J, Terhune JH, Lowenfeld L, et al. Optimizing dendritic cell-based approaches for cancer immunotherapy. Yale J Biol Med. 2014;87(4):491–518. PubMed PMID: 25506283; PubMed Central PMCID: PMC4257036.
  • Stier S, Maletzki C, Klier U, et al. Combinations of TLR ligands: a promising approach in cancer immunotherapy. Clin Dev Immunol. 2013;2013:271246. PubMed PMID: 24371445; PubMed Central PMCID: PMC3859257. DOI:10.1155/2013/271246
  • Dalod M, Chelbi R, Malissen B, et al. Dendritic cell maturation: functional specialization through signaling specificity and transcriptional programming. Embo J. 2014;33(10):1104–1116. PubMed PMID: 24737868; PubMed Central PMCID: PMC4193918. 10.1002/embj.201488027
  • Moreno Ayala M, Gottardo M, Gori M, et al. Dual activation of toll like receptors 7 and 9 impairs the efficacy of antitumor vaccines in murine models of metastatic breast cancer. J Cancer Res Clin Oncol. 2017. In press.
  • Medler TR, Cotechini T, Coussens LM. Immune response to cancer therapy: mounting an effective antitumor response and mechanisms of resistance. Trends in Cancer. 2015;1(1):66–75. PubMed PMID: 26457331; PubMed Central PMCID: PMC4594836. 10.1016/j.trecan.2015.07.008
  • Ge Y, Xi H, Ju S, et al. Blockade of PD-1/PD-L1 immune checkpoint during DC vaccination induces potent protective immunity against breast cancer in hu-SCID mice. Cancer Lett. 2013;336(2):253–259. PubMed PMID: 23523609. 10.1016/j.canlet.2013.03.010
  • Ock CY, Keam B, Kim S, et al. Pan-cancer immunogenomic perspective on the tumor microenvironment based on PD-L1 and CD8 T-cell infiltration. Clin Cancer Res. 2016; 22(9):2261–2270. PubMed PMID: 26819449. 10.1158/1078-0432.CCR-15-2834
  • Karaki S, Anson M, Tran T, et al. Is there still room for cancer vaccines at the era of checkpoint inhibitors. Vaccines. 2016;4:4. PubMed PMID: 27827885; PubMed Central PMCID: PMC5192357. DOI:10.3390/vaccines4040037
  • Safinia N, Scotta C, Vaikunthanathan T, et al. Regulatory T cells: serious contenders in the promise for immunological tolerance in transplantation. Front Immunol. 2015;6:438. PubMed PMID: 26379673; PubMed Central PMCID: PMC4553385. DOI:10.3389/fimmu.2015.00438
  • 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(5):641–648. PubMed PMID: 16960692. 10.1007/s00262-006-0225-8
  • Ge Y, Domschke C, Stoiber N, et al. Metronomic cyclophosphamide treatment in metastasized breast cancer patients: immunological effects and clinical outcome. Cancer Immunol Immunother. 2012; 61(3):353–362. PubMed PMID: 21915801. 10.1007/s00262-011-1106-3
  • Nasr KE, Osman MA, Elkady MS, et al. Metronomic methotrexate and cyclophosphamide after carboplatin included adjuvant chemotherapy in triple negative breast cancer: a phase III study. Ann Transl Med. 2015;3(19):284. PubMed PMID: 26697444; PubMed Central PMCID: PMC4671866. 10.3978/j.issn.2305-5839.2015.11.14
  • Wang X, Ren J, Zhang J, et al. Prospective study of cyclophosphamide, thiotepa, carboplatin combined with adoptive DC-CIK followed by metronomic cyclophosphamide therapy as salvage treatment for triple negative metastatic breast cancers patients (aged <45). Clin Transl Oncol. 2016; 18(1):82–87. PubMed PMID: 26266766. 10.1007/s12094-015-1339-2
  • Lien K, Georgsdottir S, Sivanathan L, et al. Low-dose metronomic chemotherapy: a systematic literature analysis. Eur J Cancer. 2013;49(16):3387–3395. PubMed PMID: 23880474. 10.1016/j.ejca.2013.06.038
  • Maiti R. Metronomic chemotherapy. J Pharmacol Pharmacother. 2014;5(3):186–192. PubMed PMID: 25210398; PubMed Central PMCID: PMC4156829. 10.4103/0976-500X.136098
  • 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. PubMed PMID: 19769742. DOI:10.1111/j.1749-6632.2009.04939.x
  • Morse MA, Hobeika AC, Osada T, et al. Depletion of human regulatory T cells specifically enhances antigen-specific immune responses to cancer vaccines. Blood. 2008; 112(3):610–618. PubMed PMID: 18519811; PubMed Central PMCID: PMC2481547. 10.1182/blood-2008-01-135319
  • Dannull J, Su Z, Rizzieri D, et al. Enhancement of vaccine-mediated antitumor immunity in cancer patients after depletion of regulatory T cells. J Clin Invest. 2005; 115(12):3623–3633. PubMed PMID: 16308572; PubMed Central PMCID: PMC1288834. 10.1172/JCI25947
  • Mahnke K, Schonfeld K, Fondel S, et al. Depletion of CD4+CD25+ human regulatory T cells in vivo: kinetics of Treg depletion and alterations in immune functions in vivo and in vitro. Int J Cancer. 2007; 120(12):2723–2733. PubMed PMID: 17315189. 10.1002/ijc.22617
  • Curtin JF, Candolfi M, Fakhouri TM, et al. Treg depletion inhibits efficacy of cancer immunotherapy: implications for clinical trials. Plos One. 2008; 3(4): e1983. Epub 2008/04/24. PubMed PMID: 18431473; PubMed Central PMCID: PMC2291560. 10.1371/journal.pone.0001983
  • Wing K, Ekmark A, Karlsson H, et al., Characterization of human CD25+ CD4+ T cells in thymus, cord and adult blood. Immunology. 2002;106(2):190–199. PubMed PMID: 12047748; PubMed Central PMCID: PMC1782718
  • Rudensky AY. Regulatory T cells and Foxp3. Immunol Rev. 2011;241(1):260–268. PubMed PMID: 21488902; PubMed Central PMCID: PMC3077798. 10.1111/j.1600-065X.2011.01018.x
  • Casares N, Rudilla F, Arribillaga L, et al. A peptide inhibitor of FOXP3 impairs regulatory T cell activity and improves vaccine efficacy in mice. J Immunology. 2010;185(9):5150–5159. PubMed PMID: 20870946. DOI:10.4049/jimmunol.1001114.
  • Moreno Ayala MG, Gottardo MF, Imsem M, et al. Therapeutic blockade of Foxp3 in experimental breast cancer models. [Manuscript in preparation]. SAIC annual meeting. Medicina 2017;76 (Suppl I):abstr376.
  • Mitchison NA, Studies on the immunological response to foreign tumor transplants in the mouse. I. The role of lymph node cells in conferring immunity by adoptive transfer. J Exp Med. 1955;102(2):157–177. PubMed PMID: 13242741; PubMed Central PMCID: PMC2136501
  • Dudley ME, Wunderlich JR, Shelton TE, et al., Generation of tumor-infiltrating lymphocyte cultures for use in adoptive transfer therapy for melanoma patients. J Immunotherapy. 2003;26(4):332–342. PubMed PMID: 12843795; PubMed Central PMCID: PMC2305721
  • Rosenberg SA, Yang JC, Sherry RM, et al. Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy. Clin Cancer Res. 2011; 17(13):4550–4557. PubMed PMID: 21498393; PubMed Central PMCID: PMC3131487. 10.1158/1078-0432.CCR-11-0116
  • Stanton SE, Disis ML. Clinical significance of tumor-infiltrating lymphocytes in breast cancer. J Immunother Cancer. 2016;4:59. PubMed PMID: 27777769. DOI:10.1186/s40425-016-0165-6
  • Laport GG, Levine BL, Stadtmauer EA, et al. Adoptive transfer of costimulated T cells induces lymphocytosis in patients with relapsed/refractory non-Hodgkin lymphoma following CD34+-selected hematopoietic cell transplantation. Blood. 2003; 102(6):2004–2013. PubMed PMID: 12763934. 10.1182/blood-2003-01-0095
  • Jena B, Dotti G, Cooper LJ. Redirecting T-cell specificity by introducing a tumor-specific chimeric antigen receptor. Blood. 2010;116(7):1035–1044. PubMed PMID: 20439624; PubMed Central PMCID: PMC2938125. 10.1182/blood-2010-01-043737
  • June CH. Adoptive T cell therapy for cancer in the clinic. J Clin Invest. 2007;117(6):1466–1476. PubMed PMID: 17549249; PubMed Central PMCID: PMC1878537. 10.1172/JCI32446
  • Domschke C, Ge Y, Bernhardt I, et al. Long-term survival after adoptive bone marrow T cell therapy of advanced metastasized breast cancer: follow-up analysis of a clinical pilot trial. Cancer Immunol Immunother. 2013; 62(6):1053–1060. PubMed PMID: 23595207. 10.1007/s00262-013-1414-x
  • Kalos M, June CH. Adoptive T cell transfer for cancer immunotherapy in the era of synthetic biology. Immunity. 2013;39(1):49–60. PubMed PMID: 23890063; PubMed Central PMCID: PMC3809038. 10.1016/j.immuni.2013.07.002
  • Posey AD Jr., Schwab RD, Boesteanu AC, et al. Engineered CAR T cells targeting the cancer-associated tn-glycoform of the membrane mucin MUC1 control adenocarcinoma. Immunity. 2016; 44(6):1444–1454. PubMed PMID: 27332733. 10.1016/j.immuni.2016.05.014
  • Wilkie S, Van Schalkwyk MC, Hobbs S, et al. Dual targeting of ErbB2 and MUC1 in breast cancer using chimeric antigen receptors engineered to provide complementary signaling. J Clin Immunol. 2012; 32(5):1059–1070. PubMed PMID: 22526592. 10.1007/s10875-012-9689-9
  • Song DG, Ye Q, Poussin M, et al. Effective adoptive immunotherapy of triple-negative breast cancer by folate receptor-alpha redirected CAR T cells is influenced by surface antigen expression level. J Hematol Oncol. 2016;9(1):56. PubMed PMID: 27439908; PubMed Central PMCID: PMC4955216. 10.1186/s13045-016-0285-y
  • Hinrichs CS, Rosenberg SA. Exploiting the curative potential of adoptive T-cell therapy for cancer. Immunol Rev. 2014;257(1):56–71. PubMed PMID: 24329789; PubMed Central PMCID: PMC3920180. 10.1111/imr.12132
  • Poschke I, Flossdorf M, Offringa R Next-generation TCR sequencing - a tool to understand T-cell infiltration in human cancers. J Pathol. 2016;240:384–386. PubMed PMID: 27569598. DOI:10.1002/path.4800
  • Vu T, Claret FX. Trastuzumab: updated mechanisms of action and resistance in breast cancer. Front Oncol. 2012;2:62. PubMed PMID: 22720269; PubMed Central PMCID: PMC3376449. DOI:10.3389/fonc.2012.00062
  • Arnould L, Gelly M, Penault-Llorca F, et al. Trastuzumab-based treatment of HER2-positive breast cancer: an antibody-dependent cellular cytotoxicity mechanism? Br J Cancer. 2006; 94(2):259–267. PubMed PMID: 16404427; PubMed Central PMCID: PMC2361112. 10.1038/sj.bjc.6602930
  • Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001; 344(11):783–792. PubMed PMID: 11248153. 10.1056/NEJM200103153441101
  • Swain SM, Baselga J, Kim SB, et al. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015; 372(8):724–734. PubMed PMID: 25693012. 10.1056/NEJMoa1413513
  • Baselga J, Gelmon KA, Verma S, et al. Phase II trial of pertuzumab and trastuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer that progressed during prior trastuzumab therapy. J Clin Oncol. 2010; 28(7):1138–1144. PubMed PMID: 20124182; PubMed Central PMCID: PMC4979216. 10.1200/JCO.2009.24.2024
  • Verma S, Miles D, Gianni L, et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med. 2012; 367(19):1783–1791. PubMed PMID: 23020162. 10.1056/NEJMoa1209124
  • Rasmussen L, Arvin A. Chemotherapy-induced immunosuppression. Environ Health Perspect. 1982;43:21–25. PubMed PMID: 7037385; PubMed Central PMCID: PMC1568884.
  • Kroemer G, Galluzzi L, Kepp O, et al. Immunogenic cell death in cancer therapy. Annu Rev Immunol. 2013;31:51–72. PubMed PMID: 23157435. DOI:10.1146/annurev-immunol-032712-100008
  • Mahmood A. Synergistic effect of dendritic cell vaccine with immune modulating chemo drugs. J Academia Ind Res (JAIR). 2015;3(12):590–597.
  • Ladoire S, Enot D, Andre F, et al. Immunogenic cell death-related biomarkers: impact on the survival of breast cancer patients after adjuvant chemotherapy. Oncoimmunology. 2016;5(2):e1082706. PubMed PMID: 27057465; PubMed Central PMCID: PMC4801435. 10.1080/2162402X.2015.1082706
  • Ladoire S, Penault-Llorca F, Senovilla L, et al. Combined evaluation of LC3B puncta and HMGB1 expression predicts residual risk of relapse after adjuvant chemotherapy in breast cancer. Autophagy. 2015; 11(10):1878–1890. PubMed PMID: 26506894; PubMed Central PMCID: PMC4824597. 10.1080/15548627.2015.1082022
  • Tsavaris N, Kosmas C, Vadiaka M, et al. Immune changes in patients with advanced breast cancer undergoing chemotherapy with taxanes. Br J Cancer. 2002;87(1):21–27. PubMed PMID: 12085250; PubMed Central PMCID: PMC2364288. 10.1038/sj.bjc.6600347
  • 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(10):3025–3030. PubMed PMID: 11595690.
  • Park JY, Jang MJ, Chung YH, et al. Doxorubicin enhances CD4(+) T-cell immune responses by inducing expression of CD40 ligand and 4-1BB. Int Immunopharmacol. 2009; 9(13–14):1530–1539. PubMed PMID: 19778641. 10.1016/j.intimp.2009.09.008
  • Hannesdottir L, Tymoszuk P, Parajuli N, et al. Lapatinib and doxorubicin enhance the Stat1-dependent antitumor immune response. Eur J Immunol. 2013; 43(10):2718–2729. PubMed PMID: 23843024. 10.1002/eji.201242505
  • Nakahara T, Uchi H, Lesokhin AM, et al. Cyclophosphamide enhances immunity by modulating the balance of dendritic cell subsets in lymphoid organs. Blood. 2010; 115(22):4384–4392. PubMed PMID: 20154220; PubMed Central PMCID: PMC2881499. 10.1182/blood-2009-11-251231
  • Le HK, Graham L, Cha E, et al. Gemcitabine directly inhibits myeloid derived suppressor cells in BALB/c mice bearing 4T1 mammary carcinoma and augments expansion of T cells from tumor-bearing mice. Int Immunopharmacol. 2009;9(7–8):900–909. PubMed PMID: 19336265. 10.1016/j.intimp.2009.03.015
  • Pfirschke C, Engblom C, Rickelt S, et al. Immunogenic chemotherapy sensitizes tumors to checkpoint blockade therapy. Immunity. 2016; 44(2):343–354. PubMed PMID: 26872698; PubMed Central PMCID: PMC4758865. 10.1016/j.immuni.2015.11.024

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