713
Views
38
CrossRef citations to date
0
Altmetric
Review

Immunotherapy for HER2-positive breast cancer: recent advances and combination therapeutic approaches

, &
Pages 53-69 | Published online: 17 Jan 2019

References

  • ChewVTohHCAbastadoJ-PImmune microenvironment in tumor progression: characteristics and challenges for therapyJ Oncol201220125110
  • Santa-MariaCAParkSJJainSGradisharWJBreast cancer and immunology: biomarker and therapeutic developmentsExpert Rev Anticancer Ther201515101215122226358181
  • SwannJBSmythMJImmune surveillance of tumorsJ Clin Invest200711751137114617476343
  • SuMHuangCXDaiAPImmune checkpoint inhibitors: therapeutic tools for breast cancerAsian Pac J Cancer Prev201617390591027039716
  • SugieTToiMAntitumor immunity and advances in cancer immunotherapyBreast Cancer20172411227882505
  • de La Cruz-MerinoLChiesaMCaballeroRBreast cancer immunology and immunotherapy: current status and future perspectivesInt Rev Cell Mol Biol201733115328325210
  • ZhangHChenJCurrent status and future directions of cancer immunotherapyJ Cancer20189101773178129805703
  • YangYCancer immunotherapy: harnessing the immune system to battle cancerJ Clin Invest201512593335333726325031
  • WojtowiczMEDunnBKUmarAImmunologic approaches to cancer prevention-current status, challenges, and future perspectivesSemin Oncol201643116117226970135
  • CriscitielloCCuriglianoGImmunotherapeutics for breast cancerCurr Opin Oncol201325660260824076578
  • PolyakKHeterogeneity in breast cancerJ Clin Invest2011121103786378821965334
  • SørlieTPerouCMTibshiraniRGene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implicationsProc Natl Acad Sci U S A20019819108691087411553815
  • PerouCMSørlieTEisenMBMolecular portraits of human breast tumoursNature2000406679774775210963602
  • AliHRProvenzanoEDawsonSJAssociation between CD8+ T-cell infiltration and breast cancer survival in 12,439 patientsAnn Oncol20142581536154324915873
  • MillerLDChouJABlackMAImmunogenic subtypes of breast cancer delineated by gene classifiers of immune responsivenessCancer Immunol Res20164760061027197066
  • MaoYQuQChenXHuangOWuJShenKThe prognostic value of tumor-infiltrating lymphocytes in breast cancer: a systematic review and meta-analysisPLoS One2016114e015250027073890
  • LoiSSirtaineNPietteFPrognostic 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 02-98J Clin Oncol201331786086723341518
  • StantonSEAdamsSDisisMLVariation in the incidence and magnitude of tumor-infiltrating lymphocytes in breast cancer subtypes: a systematic reviewJAMA Oncol20162101354136027355489
  • DenkertCvon MinckwitzGDarb-EsfahaniSTumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapyLancet Oncol2018191405029233559
  • DenkertCThe immunogenicity of breast cancer–molecular subtypes matterAnn Oncol20142581453145524950977
  • HuangYMaCZhangQCD4+ and CD8+ T cells have opposing roles in breast cancer progression and outcomeOncotarget2015619174621747825968569
  • KrishnamurtiUSilvermanJFHER2 in breast cancer: a review and updateAdv Anat Pathol201421210010724508693
  • BursteinHJThe distinctive nature of HER2-positive breast cancersN Engl J Med2005353161652165416236735
  • HudisCATrastuzumab–mechanism of action and use in clinical practiceN Engl J Med20073571395117611206
  • AhmedSSamiAXiangJHER2-directed therapy: current treatment options for HER2-positive breast cancerBreast Cancer201522210111625634227
  • SlamonDJLeyland-JonesBShakSUse of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2N Engl J Med20013441178379211248153
  • Piccart-GebhartMJProcterMLeyland-JonesBTrastuzumab after adjuvant chemotherapy in HER2-positive breast cancerN Engl J Med2005353161659167216236737
  • RomondEHPerezEABryantJTrastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancerN Engl J Med2005353161673168416236738
  • VianiGAAfonsoSLStefanoEJDe FendiLISoaresFVAdjuvant trastuzumab in the treatment of her-2-positive early breast cancer: a meta-analysis of published randomized trialsBMC Cancer20077115317686164
  • ValabregaGMontemurroFAgliettaMTrastuzumab: mechanism of action, resistance and future perspectives in HER2-overexpressing breast cancerAnn Oncol200718697798417229773
  • Amiri-KordestaniLBlumenthalGMXuQCFDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancerClin Cancer Res201420174436444124879797
  • O’SullivanCCConnollyRMPertuzumab and its accelerated approval: evolving treatment paradigms and new challenges in the management of HER2-positive breast cancerOncology201428318619424855725
  • RyanQIbrahimACohenMHFDA drug approval summary: lapatinib in combination with capecitabine for previously treated metastatic breast cancer that overexpresses HER-2Oncologist200813101114111918849320
  • SubbiahIMGonzalez-AnguloAMAdvances and future directions in the targeting of HER2-positive breast cancer: implications for the futureCurr Treat Options Oncol2014151415424323591
  • MartinMLópez-TarruellaSEmerging therapeutic options for HER2-positive breast cancerAm Soc Clin Oncol Educ Book201635e64e7027249772
  • MontemurroFDonadioMClavarezzaMOutcome of patients with HER2-positive advanced breast cancer progressing during trastuzumab-based therapyOncologist200611431832416614227
  • SalgadoRDenkertCCampbellCTumor-infiltrating lymphocytes and associations with pathological complete response and event-free survival in HER2-positive early-stage breast cancer treated with lapatinib and trastuzumabJAMA Oncology20151444845426181252
  • PerezEABallmanKVTennerKSAssociation of stromal tumor-infiltrating lymphocytes with recurrence-free survival in the n9831 adjuvant trial in patients with early-stage HER2-positive breast cancerJAMA Oncol201621566426469139
  • Ingold HeppnerBUntchMDenkertCTumor-infiltrating lymphocytes: a predictive and prognostic biomarker in neoadjuvant-treated HER2-positive breast cancerClin Cancer Res201622235747575427189162
  • LoiSMichielsSSalgadoRTumor infiltrating lymphocytes are prognostic in triple negative breast cancer and predictive for trastuzumab benefit in early breast cancer: results from the FinHER trialAnn Oncol20142581544155024608200
  • AlexeGDalginGSScanfeldDHigh expression of lymphocyte-associated genes in node-negative HER2+ breast cancers correlates with lower recurrence ratesCancer Res20076722106691067618006808
  • LuenSJSalgadoRFoxSTumour-infiltrating lymphocytes in advanced HER2-positive breast cancer treated with pertuzumab or placebo in addition to trastuzumab and docetaxel: a retrospective analysis of the CLEOPATRA studyLancet Oncol2017181526227964843
  • BenseRDSotiriouCPiccart-GebhartMJRelevance of tumor-infiltrating immune cell composition and functionality for disease outcome in breast cancerJ Natl Cancer Inst20171091djw192
  • GheybiMKFarrokhiSRavanbodMROstovarAMehrzadVNematollahiPThe correlation of CD19 + CD24 + CD38 + B cells and other clinicopathological variables with the proportion of circulating Tregs in breast cancer patientsBreast Cancer201724675676428429331
  • BailurJKGueckelBDerhovanessianEPawelecGPresence of circulating Her2-reactive CD8 + T-cells is associated with lower frequencies of myeloid-derived suppressor cells and regulatory T cells, and better survival in older breast cancer patientsBreast Cancer Res20151713425849846
  • DeckerTFischerGBückeWIncreased number of regulatory T cells (T-regs) in the peripheral blood of patients with Her-2/neupositive early breast cancerJ Cancer Res Clin Oncol2012138111945195022760213
  • VarnFSMullinsDWArias-PulidoHFieringSChengCAdaptive immunity programmes in breast cancerImmunology20171501253427564847
  • DisisMLMechanism of action of immunotherapySemin Oncol201441Suppl 5S3S13
  • SchusterMNechanskyAKircheisRCancer immunotherapyBiotechnol J20061213814716892244
  • PardollDMThe blockade of immune checkpoints in cancer immunotherapyNat Rev Cancer201212425226422437870
  • CoronaSPSobhaniNIanzaAAdvances in systemic therapy for metastatic breast cancer: future perspectivesMed Oncol201734711928526922
  • MansourMTeoZLLuenSJLoiSAdvancing immunotherapy in metastatic breast cancerCurr Treat Options Oncol20171863528534250
  • HuXHuangWFanMEmerging therapies for breast cancerJ Hematol Oncol20171019828454587
  • BuchbinderEHodiFSCytotoxic T lymphocyte antigen-4 and immune checkpoint blockadeJ Clin Invest201512593377338326325034
  • Bour-JordanHEsenstenJHMartinez-LlordellaMPenarandaCStumpfMBluestoneJAIntrinsic and extrinsic control of peripheral T-cell tolerance by costimulatory molecules of the CD28/B7 familyImmunol Rev2011241118020521488898
  • EsenstenJHHelouYAChopraGWeissABluestoneJACD28 Costimulation: from mechanism to therapyImmunity201644597398827192564
  • MccoyKDLe GrosGThe role of CTLA-4 in the regulation of T cell immune responsesImmunol Cell Biol199977111010101680
  • KarmanJJiangJLGumlawNLigation of cytotoxic T lymphocyte antigen-4 to T cell receptor inhibits T cell activation and directs differentiation into Foxp3+ regulatory T cellsJ Biol Chem201228714110981110722337882
  • EmensLABreast cancer immunobiology driving immunotherapy: vaccines and immune checkpoint blockadeExpert Rev Anticancer Ther201212121597161123253225
  • BlankCUEnkATherapeutic use of anti-CTLA-4 antibodiesInt Immunol201527131025038057
  • LipsonEJDrakeCGIpilimumab: an anti-CTLA-4 antibody for metastatic melanomaClin Cancer Res201117226958696221900389
  • GuazzelliAHussainMKrstic-DemonacosMMuttiLTremelimumab for the treatment of malignant mesotheliomaExpert Opin Biol Ther201515121819182926560442
  • McarthurHLDiabAPageDBA pilot study of preoperative single-dose ipilimumab and/or cryoablation in women with early-stage breast cancer with comprehensive immune profilingClin Cancer Res201622235729573727566765
  • VonderheideRHLorussoPMKhalilMTremelimumab in combination with exemestane in patients with advanced breast cancer and treatment-associated modulation of inducible costimulator expression on patient T cellsClin Cancer Res201016133485349420479064
  • JinHTAhmedROkazakiTRole of PD-1 in regulating T-cell immunityCurr Top Microbiol Immunol2011350173721061197
  • RileyJLPD-1 signaling in primary T cellsImmunol Rev2009229111412519426218
  • PooleRMPembrolizumab: first global approvalDrugs201474161973198125331768
  • RaedlerLAOpdivo (Nivolumab): second PD-1 inhibitor receives FDA approval for unresectable or metastatic melanomaAm Health Drug Benefits20158Spec Feature18018326629287
  • KasamonYLde ClaroRAWangYShenYLFarrellATPazdurRFDA approval summary: nivolumab for the treatment of relapsed or progressive classical Hodgkin lymphomaOncologist201722558559128438889
  • XuJXMaherVEZhangLFDA approval summary: nivolumab in advanced renal cell carcinoma after anti-angiogenic therapy and exploratory predictive biomarker analysisOncologist201722331131728232599
  • KazandjianDSuzmanDLBlumenthalGFDA approval summary: nivolumab for the treatment of metastatic non-small cell lung cancer with progression on or after platinum-based chemotherapyOncologist201621563464226984449
  • KimESAvelumab: first global approvalDrugs201777892993728456944
  • WillsSHochmuthLKBauer KsJrDeshmukhRDurvalumab: a newly approved checkpoint inhibitor for the treatment of urothelial carcinomaCurr Probl Cancer Epub2018918
  • AntoniaSJVillegasADanielDDurvalumab after chemoradiotherapy in stage III Non-Small-Cell Lung CancerN Engl J Med2017377201919192928885881
  • GhebehHMohammedSAl-OmairAThe B7-H1 (PD-L1) T lymphocyte-inhibitory molecule is expressed in breast cancer patients with infiltrating ductal carcinoma: correlation with important high-risk prognostic factorsNeoplasia20068319019816611412
  • RugoHSDelordJPImSASafety and antitumor activity of pembrolizumab in patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancerClin Cancer Res201824122804281129559561
  • NandaRChowLQDeesECPembrolizumab in patients with advanced triple-negative breast cancer: Phase Ib KEYNOTE-012 studyJ Clin Oncol201634212460246727138582
  • Emens LaBFCassierPDelordJInhibition of PD-L1 by MPDL3280A leads to clinical activity in patients with metastatic triple-negative breast cancer (TNBC). [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACRCancer Res20157515 Suppl Abstract 2859
  • SchmidPCCBraitehFSEderJPAtezolizumab in metastatic TNBC (mTNBC): Long-term clinical outcomes and biomarker analyses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACRCancer Res20177713 Suppl Abstract 2986
  • DirixLYTakacsIJerusalemGAvelumab, an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN solid tumor studyBreast Cancer Res Treat2018167367168629063313
  • LadjemiMZJacotWChardèsTPèlegrinANavarro-TeulonIAnti-HER2 vaccines: new prospects for breast cancer therapyCancer Immunol Immunother20105991295131220532501
  • PageDBNaidooJMcArthurHLEmerging immunotherapy strategies in breast cancerImmunotherapy20146219520924491092
  • ZhouJZhongYBreast cancer immunotherapyCell Mol Immunol20041424725516225767
  • RazazanABehravanJArabAConjugated nanoliposome with the HER2/neu-derived peptide GP2 as an effective vaccine against breast cancer in mice xenograft modelPLoS One20171210e018509929045460
  • CuriglianoGRescignoMGoldhirschAImmunology and breast cancer: therapeutic cancer vaccinesThe Breast200716Suppl 22026
  • CliftonGTMittendorfEAPeoplesGEAdjuvant HER2/neu peptide cancer vaccines in breast cancerImmunotherapy20157111159116826567563
  • KuznetsovaMLopatnikovaJKhantakovaJMaksyutovRMaksyutovASennikovSGeneration of populations of antigen-specific cytotoxic T cells using DCs transfected with DNA construct encoding HER2/neu tumor antigen epitopesBMC Immunol20171813128633645
  • CliftonGTPeoplesGEMittendorfEAThe development and use of the E75 (HER2 369-377) peptide vaccineFuture Oncol201612111321132927044454
  • SchnebleEJBerryJSTrappeyFAThe HER2 peptide nelipepimut-S (E75) vaccine (NeuVax™) in breast cancer patients at risk for recurrence: correlation of immunologic data with clinical responseImmunotherapy20146551953124896623
  • HuemanMTStojadinovicAStorrerCELevels of circulating regulatory CD4+CD25+ T cells are decreased in breast cancer patients after vaccination with a HER2/neu peptide (E75) and GM-CSF vaccineBreast Cancer Res Treat2006981172916758122
  • MurrayJLGilloglyMEPrzepiorkaDToxicity, immunogenicity, and induction of E75-specific tumor-lytic CTLs by HER-2 peptide E75 (369-377) combined with granulocyte macrophage colony-stimulating factor in HLA-A2+ patients with metastatic breast and ovarian cancerClin Cancer Res20028113407341812429628
  • PeoplesGEGurneyJMHuemanMTClinical trial results of a HER2/neu (E75) vaccine to prevent recurrence in high-risk breast cancer patientsJ Clin Oncol200523307536754516157940
  • MittendorfEACliftonGTHolmesJPFinal 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 patientsAnn Oncol20142591735174224907636
  • BenavidesLCGatesJDCarmichaelMGThe impact of HER2/neu expression level on response to the E75 vaccine: from U.S. Military Cancer Institute Clinical Trials Group Study I-01 and I-02Clin Cancer Res20091582895290419351776
  • MittendorfEAStorrerCEShriverCDPonniahSPeoplesGEInvestigating the combination of trastuzumab and HER2/neu peptide vaccines for the treatment of breast cancerAnn Surg Oncol20061381085109816865596
  • MittendorfEAStorrerCEFoleyRJEvaluation of the HER2/neu-derived peptide GP2 for use in a peptide-based breast cancer vaccine trialCancer2006106112309231716596621
  • CarmichaelMGBenavidesLCHolmesJPResults of the first phase 1 clinical trial of the HER-2/neu peptide (GP2) vaccine in disease-free breast cancer patients: United States Military Cancer Institute Clinical Trials Group Study I-04Cancer2010116229230119924797
  • MittendorfEAArdavanisALittonJKPrimary analysis of a prospective, randomized, single-blinded phase II trial evaluating the HER2 peptide GP2 vaccine in breast cancer patients to prevent recurrenceOncotarget2016740661926620127589688
  • GatesJDCliftonGTBenavidesLCCirculating regulatory T cells (CD4+CD25+FOXP3+) decrease in breast cancer patients after vaccination with a modified MHC class II HER2/neu (AE37) peptideVaccine201028477476748220858449
  • HolmesJPBenavidesLCGatesJDResults of the first phase I clinical trial of the novel II-key hybrid preventive HER-2/neu peptide (AE37) vaccineJ Clin Oncol200826203426343318612158
  • MittendorfEAArdavanisASymanowskiJPrimary analysis of a prospective, randomized, single-blinded phase II trial evaluating the HER2 peptide AE37 vaccine in breast cancer patients to prevent recurrenceAnn Oncol20162771241124827029708
  • Abdel-AalABLakshminarayananVThompsonPImmune and anticancer responses elicited by fully synthetic aberrantly glycosylated MUC1 tripartite vaccines modified by a TLR2 or TLR9 agonistChembiochem201415101508151324890740
  • BafnaSKaurSBatraSKMembrane-bound mucins: the mechanistic basis for alterations in the growth and survival of cancer cellsOncogene201029202893290420348949
  • KimuraTFinnOJMUC1 immunotherapy is here to stayExpert Opin Biol Ther2013131354922998452
  • YuanSShiCLiuLHanWMUC1-based recombinant Bacillus Calmette-Guerin vaccines as candidates for breast cancer immunotherapyExpert Opin Biol Ther20101071037104820420512
  • ApostolopoulosVPieterszGATsibanisAPilot phase III immunotherapy study in early-stage breast cancer patients using oxidized mannan-MUC1 [ISRCTN71711835]Breast Cancer Res200683R2716776849
  • VassilarosSTsibanisATsikkinisAPieterszGAMckenzieIFApostolopoulosVUp to 15-year clinical follow-up of a pilot Phase III immunotherapy study in stage II breast cancer patients using oxidized mannan-MUC1Immunotherapy20135111177118224188672
  • Al JoudiFSHuman mammaglobin in breast cancer: a brief review of its clinical utilityIndian J Med Res2014139567568525027076
  • KimSWGoedegebuurePGillandersWEMammaglobin-A is a target for breast cancer vaccinationOncoimmunology201652e106994027057470
  • TiriveedhiVFlemingTPGoedegebuurePSMammaglobin-A cDNA vaccination of breast cancer patients induces antigen-specific cytotoxic CD4+ICOShi T cellsBreast Cancer Res Treat2013138110911822678162
  • TiriveedhiVTuckerNHerndonJSafety and preliminary evidence of biologic efficacy of a mammaglobin-a DNA vaccine in patients with stable metastatic breast cancerClin Cancer Res201420235964597525451106
  • ChenYEmtagePZhuQInduction of ErbB-2/neu-specific protective and therapeutic antitumor immunity using genetically modified dendritic cells: enhanced efficacy by cotransduction of gene encoding IL-12Gene Ther20018431632311313806
  • SasSChanTSamiAEl-GayedAXiangJVaccination of fiber-modified adenovirus-transfected dendritic cells to express HER-2/neu stimulates efficient HER-2/neu-specific humoral and CTL responses and reduces breast carcinogenesis in transgenic miceCancer Gene Ther2008151065566618421311
  • BrossartPWirthsSStuhlerGReichardtVLKanzLBruggerWInduction of cytotoxic T-lymphocyte responses in vivo after vaccinations with peptide-pulsed dendritic cellsBlood20009693102310811049990
  • CzernieckiBJKoskiGKKoldovskyUTargeting HER-2/neu in early breast cancer development using dendritic cells with staged interleukin-12 burst secretionCancer Res20076741842185217293384
  • KoskiGKKoldovskyUXuSA novel dendritic cell-based immunization approach for the induction of durable Th1-polarized anti-HER-2/neu responses in women with early breast cancerJ Immunother2012351546522130160
  • SharmaAKoldovskyUXuSHER-2 pulsed dendritic cell vaccine can eliminate HER-2 expression and impact ductal carcinoma in situCancer2012118174354436222252842
  • LowenfeldLMickRDattaJDendritic cell vaccination enhances immune responses and induces regression of HER2pos DCIS independent of route: results of randomized selection design trialClin Cancer Res201723122961297127965306
  • KalosMJuneCHAdoptive T cell transfer for cancer immunotherapy in the era of synthetic biologyImmunity2013391496023890063
  • PericaKVarelaJCOelkeMSchneckJAdoptive T cell immunotherapy for cancerRambam Maimonides Med J201561e000425717386
  • TchouJWangLCSelvenBMesothelin, a novel immunotherapy target for triple negative breast cancerBreast Cancer Res Treat2012133279980422418702
  • LerretNMRogozinskaMJaramilloAMarzoALAdoptive transfer of Mammaglobin-A epitope specific CD8 T cells combined with a single low dose of total body irradiation eradicates breast tumorsPLoS One201277e4124022911764
  • WilkieSvan SchalkwykMCHobbsSDual targeting of ErbB2 and MUC1 in breast cancer using chimeric antigen receptors engineered to provide complementary signalingJ Clin Immunol20123251059107022526592
  • LanitisESmithJBDangajDA human ErbB2-specific T-cell receptor confers potent antitumor effector functions in genetically engineered primary cytotoxic lymphocytesHum Gene Ther201425873073925003657
  • LiSYangJUrbanFAGenetically engineered T cells expressing a HER2-specific chimeric receptor mediate antigen-specific tumor regressionCancer Gene Ther200815638239218292797
  • MoralesJKKmieciakMGrahamLFeldmesserMBearHDManjiliMHAdoptive transfer of HER2/neu-specific T cells expanded with alternating gamma chain cytokines mediate tumor regression when combined with the depletion of myeloid-derived suppressor cellsCancer Immunol Immunother200958694195318979098
  • WangLXPlautzGET cells sensitized with breast tumor progenitor cell vaccine have therapeutic activity against spontaneous HER2/neu tumorsBreast Cancer Res Treat20121341617022173696
  • BernhardHNeudorferJGebhardKAdoptive transfer of autologous, HER2-specific, cytotoxic T lymphocytes for the treatment of HER2-overexpressing breast cancerCancer Immunol Immunother200757227128017646988
  • RobertLRibasAHu-LieskovanSCombining targeted therapy with immunotherapy. Can 1+1 equal more than 2?Semin Immunol2016281738026861544
  • GotwalsPCameronSCipollettaDProspects for combining targeted and conventional cancer therapy with immunotherapyNat Rev Cancer201717528630128338065
  • WargoJAReubenACooperZAOhKSSullivanRJImmune effects of chemotherapy, radiation, and targeted therapy and opportunities for combination with immunotherapySemin Oncol201542460161626320064
  • VonderheideRHDomchekSMClarkASImmunotherapy for Breast Cancer: What Are We Missing?Clin Cancer Res201723112640264628572258
  • XiaQZhangFFGengFImprovement of anti-tumor immunity of fibroblast activation protein α based vaccines by combination with cyclophosphamide in a murine model of breast cancerCell Immunol2016310899827545090
  • MadondoMTQuinnMPlebanskiMLow dose cyclophosphamide: mechanisms of T cell modulationCancer Treat Rev2016423926620820
  • KarevaIA Combination of immune checkpoint inhibition with metronomic chemotherapy as a way of targeting therapy-resistant cancer cellsInt J Mol Sci20171810E213429027915
  • ZhuXJYangZFZhouJYProgression of large lymphoma is significantly impeded with a combination of gemcitabine chemotherapy and dendritic cells intra-tumor vaccinationPLoS One2015107e013279926181041
  • BanissiCGhiringhelliFChenLCarpentierAFTreg depletion with a low-dose metronomic temozolomide regimen in a rat glioma modelCancer Immunol Immunother200958101627163419221744
  • GhiringhelliFMenardCPuigPEMetronomic cyclophosphamide regimen selectively depletes CD4+CD25+ regulatory T cells and restores T and NK effector functions in end stage cancer patientsCancer Immunol Immunother200756564164816960692
  • ChagantyBKRQiuSGestATrastuzumab upregulates PD-L1 as a potential mechanism of trastuzumab resistance through engagement of immune effector cells and stimulation of IFNγ secretionCancer Lett2018430475629746929
  • JunttilaTTLiJJohnstonJAntitumor efficacy of a bispecific antibody that targets HER2 and activates T cellsCancer Res201474195561557125228655
  • ForceJHowieLJAbbottSEEarly stage HER2-positive breast cancers not achieving a pcr from neoadjuvant trastuzumab- or pertuzumab-based regimens have an immunosuppressive phenotypeClin Breast Cancer201818541041729615305
  • YeJCFormentiSCIntegration of radiation and immunotherapy in breast cancer – treatment implicationsBreast201838667429253718
  • HuZIHoAYMcArthurHLCombined radiation therapy and immune checkpoint blockade therapy for breast cancerInt J Radiat Oncol Biol Phys201799115316428816141
  • IshiharaDPopLTakeshimaTIyengarPHannanRRationale and evidence to combine radiation therapy and immunotherapy for cancer treatmentCancer Immunol Immunother201766328129827743027