Open Access

Reinstating endogenous antitumor immunity: The concept of therapeutic management of cancer


Cite

Sharma, P. and J.P. Allison, The future of immune checkpoint therapy. Science, 2015. 348(6230): p. 56-61.SharmaP.AllisonJ.P.The future of immune checkpoint therapyScience20153486230566110.1126/science.aaa817225838373Search in Google Scholar

Dunn, G.P., C.M. Koebel, and R.D. Schreiber, Interferons, immunity and cancer immunoediting. Nat Rev Immunol, 2006. 6(11): p. 836-48.DunnG.P.KoebelC.M.SchreiberR.D.Interferons, immunity and cancer immunoeditingNat Rev Immunol20066118364810.1038/nri196117063185Search in Google Scholar

Galon, J., Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorc-Pages C, et al., Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science, 2006. 313(5795): p. 1960-4.GalonJ.CostesASanchez-CaboFKirilovskyAMlecnikBLagorc-PagesCet al.Type, density, and location of immune cells within human colorectal tumors predict clinical outcomeScience200631357951960410.1126/science.112913917008531Search in Google Scholar

Schreiber R.D., Old LJ, Smyth ML, Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science. 2011 Mar 25;331(6024):1565-70SchreiberR.D.OldLJSmythMLCancer immunoediting: integrating immunity’s roles in cancer suppression and promotionScience2011Mar25331602415657010.1126/science.120348621436444Search in Google Scholar

Galon, J., Pages F, Marincola FM, Angell HK, Thurin M, Lugli A, et al., Cancer classification using the Immunoscore: a worldwide task force. J Transl Med, 2012 Oct 3;10: p. 205.GalonJ.PagesFMarincolaFMAngellHKThurinMLugliAet al.Cancer classification using the Immunoscore: a worldwide task forceJ Transl Med2012Oct310205Search in Google Scholar

Galon, J., Mlecnik B, Bindea G, Angell HK, Berger A, Lagorce C, et al., Towards the introduction of the ‘Immunoscore’ in the classification of malignant tumours. J Pathol, 2014. 232(2): p. 199-209.GalonJ.MlecnikBBindeaGAngellHKBergerALagorceCet al.Towards the introduction of the ‘Immunoscore’ in the classification of malignant tumoursJ Pathol2014232219920910.1002/path.4287425530624122236Search in Google Scholar

Baxevanis, C.N., M. Papamichail, and S.A. Perez, Immune classification of colorectal cancer patients: impressive but how complete? Expert OpinBiolTher, 2013. 13(4): p. 517-26.BaxevanisC.N.PapamichailM.PerezS.A.Immune classification of colorectal cancer patients: impressive but how complete?Expert OpinBiolTher201313451726Search in Google Scholar

Becht, E., Giraldo NA, Dieu-Nosjean MC, Sautès-Fridman C, Fridman WH, Cancer immune contexture and immunotherapy. CurrOpinImmunol, 2015. 39: p. 7-13BechtE.GiraldoNADieu-NosjeanMCSautès-FridmanCFridmanWHCancer immune contexture and immunotherapyCurrOpinImmunol20153971310.1016/j.coi.2015.11.00926708937Search in Google Scholar

Krummel, M.F. and J.P. Allison, CTLA-4 engagement inhibits IL-2 accumulation and cell cycle progression upon activation of resting T cells. J Exp Med, 1996. 183(6): p. 2533-40.KrummelM.F.AllisonJ.P.CTLA-4 engagement inhibits IL-2 accumulation and cell cycle progression upon activation of resting T cellsJ Exp Med1996183625334010.1084/jem.183.6.253321926138676074Search in Google Scholar

Pardoll, D.M., The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer, 2012. 12(4): p. 252-64.PardollD.M.The blockade of immune checkpoints in cancer immunotherapyNat Rev Cancer20121242526410.1038/nrc3239485602322437870Search in Google Scholar

Schneider, H., Downey J, Smith A, Zinselmeyer BH, Rush C, Brewer JM, et al., Reversal of the TCR stop signal by CTLA-4. Science, 2006. 313(5795): p. 1972-5.SchneiderH.DowneyJSmithAZinselmeyerBHRushCBrewerJMet al.Reversal of the TCR stop signal by CTLA-4Science200631357951972510.1126/science.113107816931720Search in Google Scholar

Qureshi, O.S., Zheng Y, Nakamura K, Attridge K, Manzotti C, Schmidt EM, Baker J, et al., Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4. Science, 2011. 332(6029): p. 600-3.QureshiO.S.ZhengYNakamuraKAttridgeKManzottiCSchmidtEMBakerJet al.Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4Science20113326029600310.1126/science.1202947319805121474713Search in Google Scholar

Fecher, L.A., Agarwala SS, Hodi FS, Weber JS:Ipilimumab and its toxicities: a multidisciplinary approach. Oncologist, 2013. 18(6): p. 733-43.FecherL.A.AgarwalaSSHodiFSWeberJSIpilimumab and its toxicities: a multidisciplinary approachOncologist20131867334310.1634/theoncologist.2012-0483406340123774827Search in Google Scholar

Ivashko, I.N. and J.M. Kolesar, Pembrolizumab and nivolumab: PD-1 inhibitors for advanced melanoma. Am J Health Syst Pharm, 2016. 73(4): p. 193-201.IvashkoI.N.KolesarJ.M.Pembrolizumab and nivolumab: PD-1 inhibitors for advanced melanomaAm J Health Syst Pharm201673419320110.2146/ajhp14076826843495Search in Google Scholar

Topalian, S.L., Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, et al., Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med, 2012. 366(26): p. 2443-54.TopalianS.L.HodiFSBrahmerJRGettingerSNSmithDCMcDermottDFet al.Safety, activity, and immune correlates of anti-PD-1 antibody in cancerN Engl J Med20123662624435410.1056/NEJMoa1200690354453922658127Search in Google Scholar

Hamid, O., Robert C, Daud A, Hodi FS, Hwu WJ, Kefford R, et al., Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med, 2013. 369(2): p. 134-44.HamidO.RobertCDaudAHodiFSHwuWJKeffordRet al.Safety and tumor responses with lambrolizumab (anti-PD-1) in melanomaN Engl J Med201336921344410.1056/NEJMoa1305133412651623724846Search in Google Scholar

Butte, M.J., 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): p. 111-22.ButteM.J.KeirMEPhamduyTBSharpeAHFreemanGJ.Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responsesImmunity20072711112210.1016/j.immuni.2007.05.016270794417629517Search in Google Scholar

Brahmer, J.R., Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, et al., Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med, 2012. 366(26): p. 2455-65.BrahmerJ.R.TykodiSSChowLQHwuWJTopalianSLHwuPet al.Safety and activity of anti-PD-L1 antibody in patients with advanced cancerN Engl J Med20123662624556510.1056/NEJMoa1200694356326322658128Search in Google Scholar

Taube, J.M., Anders RA, Young GD, Xu H, Sharma R, McMiller TL, et al., Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Sci Transl Med, 2012. 4(127): p. 127ra37.TaubeJ.M.AndersRAYoungGDXuHSharmaRMcMillerTLet al.Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escapeSci Transl Med20124127127ra3710.1126/scitranslmed.3003689356852322461641Search in Google Scholar

Herbst, R.S., Soria JC, Kowanetz M, Fine GD, Hamid O, Gordon MS, et al., Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature, 2014. 515(7528): p. 563-7.HerbstR.S.SoriaJCKowanetzMFineGDHamidOGordonMSet al.Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patientsNature20145157528563710.1038/nature14011483619325428504Search in Google Scholar

Llosa, N.J., Cruise M, Tam A, Wicks EC, Hechenbleikner EM, Taube JM et al., The vigorous immune microenvironment of microsatellite instable colon cancer is balanced by multiple counter-inhibitory checkpoints. Cancer Discov, 2015. 5(1): p. 43-51.LlosaN.J.CruiseMTamAWicksECHechenbleiknerEMTaubeJMet al.The vigorous immune microenvironment of microsatellite instable colon cancer is balanced by multiple counter-inhibitory checkpointsCancer Discov201551435110.1158/2159-8290.CD-14-0863429324625358689Search in Google Scholar

Powles, T., Eder JP, Fine GD, Braiteh FS, Loriot Y, Cruz C, et al., MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature, 2014. 515(7528): p. 558-62.PowlesT.EderJPFineGDBraitehFSLoriotYCruzCet al.MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancerNature201451575285586210.1038/nature1390425428503Search in Google Scholar

Rizvi, N.A., Hellmann MD, Snyder A, Kvistborg P, Makarov V, Havel JJ, et al., Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science, 2015. 348(6230): p. 124-8.RizviN.A.HellmannMDSnyderAKvistborgPMakarovVHavelJJet al.Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancerScience20153486230124810.1126/science.aaa1348499315425765070Search in Google Scholar

Taube, J.M., Klein A, Brahmer JR, Xu H, Pan X, Kim JH, et al., Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti-PD-1 therapy. Clin Cancer Res, 2014. 20(19): p. 5064-74.TaubeJ.M.KleinABrahmerJRXuHPanXKimJHet al.Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti-PD-1 therapyClin Cancer Res2014201950647410.1158/1078-0432.CCR-13-3271418500124714771Search in Google Scholar

Carbognin, L., Pilotto S, Milella M, Vaccaro V, Brunelli M, Caliò A, et al., Differential Activity of Nivolumab, Pembrolizumab and MPDL3280A according to the Tumor Expression of Programmed Death-Ligand-1 (PD-L1): Sensitivity Analysis of Trials in Melanoma, Lung and Genitourinary Cancers. PLoS One, 2015. 10(6): p. e0130142.CarbogninL.PilottoSMilellaMVaccaroVBrunelliMCaliòAet al.Differential Activity of Nivolumab, Pembrolizumab and MPDL3280A according to the Tumor Expression of Programmed Death-Ligand-1 (PD-L1): Sensitivity Analysis of Trials in Melanoma, Lung and Genitourinary CancersPLoS One2015106e013014210.1371/journal.pone.0130142447278626086854Search in Google Scholar

Gainor, J., et al., Clinical correlation and frequency of programmed death ligand-1 (PD-L1) expression in EGFR-mutant and ALK-rearranged non-small cell lung cancer (NSCLC). J Clin Oncol 2015. 33(_suppl): p. abstr 8012.GainorJ.et al.Clinical correlation and frequency of programmed death ligand-1 (PD-L1) expression in EGFR-mutant and ALK-rearranged non-small cell lung cancer (NSCLC)J Clin Oncol201533_supplp. abstr801210.1200/jco.2015.33.15_suppl.8012Search in Google Scholar

Watson, I.R., Takahashi K, Futreal PA, Chin L., Emerging patterns of somatic mutations in cancer. Nat Rev Genet, 2013. 14(10): p. 703-18.WatsonI.R.TakahashiKFutrealPAChinL.Emerging patterns of somatic mutations in cancerNat Rev Genet201314107031810.1038/nrg3539401435224022702Search in Google Scholar

Yadav, M., Jhunjhunwala S, Phung QT, Lupardus P, Tanguay J, Bumbaca S, et al., Predicting immunogenic tumour mutations by combining mass spectrometry and exome sequencing. Nature, 2014. 515(7528): p. 572-6.YadavM.JhunjhunwalaSPhungQTLupardusPTanguayJBumbacaSet al.Predicting immunogenic tumour mutations by combining mass spectrometry and exome sequencingNature20145157528572610.1038/nature1400125428506Search in Google Scholar

Schumacher, T.N. and R.D. Schreiber, Neoantigens in cancer immunotherapy. Science, 2015. 348(6230): p. 69-74.SchumacherT.N.SchreiberR.D.Neoantigens in cancer immunotherapyScience20153486230697410.1126/science.aaa497125838375Search in Google Scholar

Gubin, M.M., Zhang X, Schuster H, Caron E, Ward JP, Noguchi T, et al., Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens. Nature, 2014. 515(7528): p. 577-81.GubinM.M.ZhangXSchusterHCaronEWardJPNoguchiTet al.Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigensNature201451575285778110.1038/nature13988427995225428507Search in Google Scholar

Boussiotis, V.A., Somatic mutations and immunotherapy outcome with CTLA-4 blockade in melanoma. N Engl J Med, 2014. 371(23): p. 2230-2.BoussiotisV.A.Somatic mutations and immunotherapy outcome with CTLA-4 blockade in melanomaN Engl J Med2014371232230210.1056/NEJMe1413061445667725409261Search in Google Scholar

Snyder, A., Makarov V, Merghoub T, Yuan J, Zaretsky JM, Desrichard A, et al., Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med, 2014. 371(23): p. 2189-99.SnyderA.MakarovVMerghoubTYuanJZaretskyJMDesrichardAet al.Genetic basis for clinical response to CTLA-4 blockade in melanomaN Engl J Med20143712321899910.1056/NEJMoa1406498431531925409260Search in Google Scholar

Lawrence, M.S., Stojanov P, Polak P, Kryukov GV, Cibulskis K, Sivachenko A, et al., Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature, 2013. 499(7457): p. 214-8.LawrenceM.S.StojanovPPolakPKryukovGVCibulskisKSivachenkoAet al.Mutational heterogeneity in cancer and the search for new cancer-associated genesNature20134997457214810.1038/nature12213Search in Google Scholar

Guinney, J., Dienstmann R, Wang X, de Reyniès A, Schlicker A, Soneson C, et al., The consensus molecular subtypes of colorectal cancer. Nat Med, 2015. 21(11): p. 1350-6.GuinneyJ.DienstmannRWangXde ReynièsASchlickerASonesonCet al.The consensus molecular subtypes of colorectal cancerNat Med201521111350610.1038/nm.3967Search in Google Scholar

Segal, N.H. and L.B. Saltz, Translational considerations on the outlook of immunotherapy for colorectal cancer. Curr Colorectal Cancer Rep 2015. 11: p. 92-97.SegalN.H.SaltzL.B.Translational considerations on the outlook of immunotherapy for colorectal cancerCurr Colorectal Cancer Rep201511929710.1007/s11888-015-0258-5Search in Google Scholar

Wang, J., Tang C, Zhang L, Gong Y, Yin C, Li Y, Compressing with dominant hand improves quality of manual chest compressions for rescuers who performed suboptimal CPR in manikins. Am J Emerg Med, 2015. 33(7): p. 931-6.WangJ.TangCZhangLGongYYinCLiYCompressing with dominant hand improves quality of manual chest compressions for rescuers who performed suboptimal CPR in manikinsAm J Emerg Med2015337931610.1016/j.ajem.2015.04.007Search in Google Scholar

Le, D.T., 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): p. 2509-20.LeD.T.UramJNWangHBartlettBRKemberlingHEyringADet al.PD-1 Blockade in Tumors with Mismatch-Repair DeficiencyN Engl J Med20153722625092010.1056/NEJMoa1500596Search in Google Scholar

Chia, N.Y. and P. Tan, Molecular Classification of Gastric Cancer. Ann Oncol, 2016.ChiaN.Y.TanP.Molecular Classification of Gastric CancerAnn Oncol201610.1093/annonc/mdw040Search in Google Scholar

Muro, K., et al., Relationship between PD-L1 expression and clinical outcomes in patients (Pts) with advanced gastric cancer treated with the anti-PD-1 monoclonal antibody pembrolizumab (Pembro; MK-3475) in KEYNOTE-0120.. J Clin Oncol, 2015. 33(3_suppl): p. 3.MuroK.et al.Relationship between PD-L1 expression and clinical outcomes in patients (Pts) with advanced gastric cancer treated with the anti-PD-1 monoclonal antibody pembrolizumab (Pembro; MK-3475) in KEYNOTE-012J Clin Oncol2015333_suppl310.1200/jco.2015.33.3_suppl.3Search in Google Scholar

Ott, P., et al., Pembrolizumab (MK-3475) For PD-L1–Positive Squamous Cell Carcinoma of the Anal Canal: Preliminary Safety and Efficacy Results From KEYNOTE-028. Eur J Cancer, 2015. 51(3_suppl): p. abstr 500.OttP.et al.Pembrolizumab (MK-3475) For PD-L1–Positive Squamous Cell Carcinoma of the Anal Canal: Preliminary Safety and Efficacy Results From KEYNOTE-028Eur J Cancer2015513_supplabstr50010.1016/S0959-8049(15)30008-3Search in Google Scholar

Fearon, D.T., The carcinoma-associated fibroblast expressing fibroblast activation protein and escape from immune surveillance. Cancer Immunol Res, 2014. 2(3): p. 187-93.FearonD.T.The carcinoma-associated fibroblast expressing fibroblast activation protein and escape from immune surveillanceCancer Immunol Res2014231879310.1158/2326-6066.CIR-14-000224778314Search in Google Scholar

Le, D.T., Wang-Gillam A, Picozzi V, Greten TF, Crocenzi T, Springett G, et al., Safety and survival with GVAX pancreas prime and Listeria Monocytogenes-expressing mesothelin (CRS-207) boost vaccines for metastatic pancreatic cancer. J Clin Oncol, 2015. 33(12): p. 1325-33.LeD.T.Wang-GillamAPicozziVGretenTFCrocenziTSpringettGet al.Safety and survival with GVAX pancreas prime and Listeria Monocytogenes-expressing mesothelin (CRS-207) boost vaccines for metastatic pancreatic cancerJ Clin Oncol2015331213253310.1200/JCO.2014.57.4244439727725584002Search in Google Scholar

El-Khoueiry, A., et al., Phase I/II Safety and Antitumor Activity of Nivolumab in Patients with Advanced Hepatocellular Carcinoma (HCC): CA209-040. J Clin Oncol, 2015. 33(_suppl): p. abstr LBA101.El-KhoueiryA.et al.Phase I/II Safety and Antitumor Activity of Nivolumab in Patients with Advanced Hepatocellular Carcinoma (HCC): CA209-040J Clin Oncol201533_supplp. abstr LBA10110.1200/jco.2015.33.18_suppl.lba101Search in Google Scholar

Coosemans, A., T. Baert, and I. Vergote, A view on dendritic cell immunotherapy in ovarian cancer: how far have we come? Facts Views Vis Obgyn, 2015. 7(1): p. 73-8.CoosemansA.BaertT.VergoteI.A view on dendritic cell immunotherapy in ovarian cancer: how far have we come?Facts Views Vis Obgyn201571738Search in Google Scholar

Hamanishi, J., Mandai M, Ikeda T, Minami M, Kawaguchi A, Murayama T, et al., Safety and Antitumor Activity of Anti-PD-1 Antibody, Nivolumab, in Patients With Platinum-Resistant Ovarian Cancer. J Clin Oncol, 2015. 33(34): p. 4015-22.HamanishiJ.MandaiMIkedaTMinamiMKawaguchiAMurayamaTet al.Safety and Antitumor Activity of Anti-PD-1 Antibody, Nivolumab, in Patients With Platinum-Resistant Ovarian CancerJ Clin Oncol2015333440152210.1200/JCO.2015.62.3397Search in Google Scholar

Sato, E., Olson SH, Ahn J, Bundy B, Nishikawa H, Qian F, et al., Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc Natl Acad Sci U S A, 2005. 102(51): p. 18538-43.SatoE.OlsonSHAhnJBundyBNishikawaHQianFet al.Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancerProc Natl Acad Sci U S A200510251185384310.1073/pnas.0509182102Search in Google Scholar

Vermeij, R., Leffers N, Hoogeboom BN, Hamming IL, Wolf R, Reyners AK, et al., Potentiation of a p53-SLP vaccine by cyclophosphamide in ovarian cancer: a single-arm phase II study. Int J Cancer, 2012. 131(5): p. E670-80.VermeijR.LeffersNHoogeboomBNHammingILWolfRReynersAKet al.Potentiation of a p53-SLP vaccine by cyclophosphamide in ovarian cancer: a single-arm phase II studyInt J Cancer20121315E6708010.1002/ijc.27388Search in Google Scholar

Disis, M.L., et al: Avelumab (MSB0010718C), an anti-PD-L1 antibody, in patients with previously treated, recurrent or refractory ovarian cancer: A phase Ib, open-label expansion trial. J ClinOncol 33, 2015 (suppl; abstr 5509)DisisM.L.et alAvelumab (MSB0010718C), an anti-PD-L1 antibody, in patients with previously treated, recurrent or refractory ovarian cancer: A phase Ib, open-label expansion trialJ ClinOncol 332015suppl; abstr 550910.1200/jco.2015.33.15_suppl.5509Search in Google Scholar

Motzer, R.J., 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): p. 1803-13.MotzerR.J.EscudierBMcDermottDFGeorgeSHammersHJSrinivasSet al.Nivolumab versus Everolimus in Advanced Renal-Cell CarcinomaN Engl J Med20153731918031310.1056/NEJMoa1510665Search in Google Scholar

O’Donnell, P., E. Plimack, and J. Bellmunt, Pembrolizumab (Pembro; MK-3475) for advanced urothelial cancer: Results of a phase IB study. J Clin Oncol 2015. 33(7_suppl): p. abstr 296.O’DonnellP.PlimackE.BellmuntJ.Pembrolizumab (Pembro; MK-3475) for advanced urothelial cancer: Results of a phase IB studyJ Clin Oncol2015337_suppl29610.1200/jco.2015.33.7_suppl.296Search in Google Scholar

Rosenberg, J., et al., 21LBA Atezolizumab in patients (pts) with locally-advanced or metastatic urothelial carcinoma (mUC): Results from a pivotal multicenter phase II study (IMvigor 21) Eur J Cancer, 2015. 51(3_suppl): p. S120.RosenbergJ.et al.21LBA Atezolizumab in patients (pts) with locally-advanced or metastatic urothelial carcinoma (mUC): Results from a pivotal multicenter phase II study (IMvigor 21)Eur J Cancer2015513_supplS12010.1016/S0959-8049(16)31942-6Search in Google Scholar

Rosenberg, J., Hoffman-Censits J, Powles T, van der Heijden MS, Balar AV, Necchi A, et al: Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet, 7 May 2016, vol387;10031:1909-1920RosenbergJ.Hoffman-CensitsJPowlesTvan der HeijdenMSBalarAVNecchiAet alAtezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trialLancet7May2016387100311909192010.1016/S0140-6736(16)00561-4Search in Google Scholar

Andrews, D.M., E. Maraskovsky, and M.J. Smyth, Cancer vaccines for established cancer: how to make them better? Immunol Rev, 2008. 222: p. 242-55.AndrewsD.M.MaraskovskyE.SmythM.J.Cancer vaccines for established cancer: how to make them better?Immunol Rev200822224255Search in Google Scholar

GuhaThakurta, D., Sheikh NA, Fan LQ, Kandadi H, Meagher TC, Hall SJ, et al., Humoral Immune Response against Non-targeted Tumor Antigens after Treatment with Sipuleucel-T and Its Association with Improved Clinical Outcome. Clin Cancer Res, 2015. 21(16): p. 3619-30.GuhaThakurtaD.SheikhNAFanLQKandadiHMeagherTCHallSJet al.Humoral Immune Response against Non-targeted Tumor Antigens after Treatment with Sipuleucel-T and Its Association with Improved Clinical OutcomeClin Cancer Res2015211636193010.1158/1078-0432.CCR-14-2334486805425649018Search in Google Scholar

Kantoff, P.W., Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, et al., Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med, 2010. 363(5): p. 411-22.KantoffP.W.HiganoCSShoreNDBergerERSmallEJPensonDFet al.Sipuleucel-T immunotherapy for castration-resistant prostate cancerN Engl J Med201036354112210.1056/NEJMoa100129420818862Search in Google Scholar

Sheikh, N.A., Petrylak D, Kantoff PW, Dela Rosa C, Stewart FP, Kuan LY, et al., Sipuleucel-T immune parameters correlate with survival: an analysis of the randomized phase 3 clinical trials in men with castration-resistant prostate cancer. Cancer Immunol Immunother, 2013. 62(1): p. 137-47.SheikhN.A.PetrylakDKantoffPWDela RosaCStewartFPKuanLYet al.Sipuleucel-T immune parameters correlate with survival: an analysis of the randomized phase 3 clinical trials in men with castration-resistant prostate cancerCancer Immunol Immunother20136211374710.1007/s00262-012-1317-2354192622865266Search in Google Scholar

Park, J.W., Melisko ME, Esserman LJ, Jones LA, Wollan JB, Sims R., 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): p. 3680-7.ParkJ.W.MeliskoMEEssermanLJJonesLAWollanJBSimsR.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 cancerJ Clin Oncol200725243680710.1200/JCO.2006.10.571817704416Search in Google Scholar

Senzer, N. and J. Nemunaitis, A review of contusugeneladenovec (Advexin) p53 therapy. CurrOpinMolTher, 2009. 11(1): p. 54-61.SenzerN.NemunaitisJ.A review of contusugeneladenovec (Advexin) p53 therapyCurrOpinMolTher20091115461Search in Google Scholar

Kantoff, P.W., Schuetz TJ, Blumenstein BA, Glode LM, Bilhartz DL, Wyand M, et al., Overall survival analysis of a phase II randomized controlled trial of a Poxviral-based PSA-targeted immunotherapy in metastatic castration-resistant prostate cancer. J Clin Oncol, 2010. 28(7): p. 1099-105.KantoffP.W.SchuetzTJBlumensteinBAGlodeLMBilhartzDLWyandMet al.Overall survival analysis of a phase II randomized controlled trial of a Poxviral-based PSA-targeted immunotherapy in metastatic castration-resistant prostate cancerJ Clin Oncol2010287109910510.1200/JCO.2009.25.0597283446220100959Search in Google Scholar

Gulley, J.L., Arlen PM, Madan RA, Tsang KY, Pazdur MP, Skarupa L, et al., Immunologic and prognostic factors associated with overall survival employing a poxviral-based PSA vaccine in metastatic castrate-resistant prostate cancer. Cancer Immunol Immunother, 2010. 59(5): p. 663-74.GulleyJ.L.ArlenPMMadanRATsangKYPazdurMPSkarupaLet al.Immunologic and prognostic factors associated with overall survival employing a poxviral-based PSA vaccine in metastatic castrate-resistant prostate cancerCancer Immunol Immunother20105956637410.1007/s00262-009-0782-8283208319890632Search in Google Scholar

Garnett, C.T., Greiner JW, Tsang KY, Kudo-Saito C, Grosenbach DW, Chakraborty M, et al., TRICOM vector based cancer vaccines. Curr Pharm Des, 2006. 12(3): p. 351-61.GarnettC.T.GreinerJWTsangKYKudo-SaitoCGrosenbachDWChakrabortyMet al.TRICOM vector based cancer vaccinesCurr Pharm Des20061233516110.2174/13816120677520192916454749Search in Google Scholar

Gulley, J.L., Arlen PM, Tsang KY, Yokokawa J, Palena C, Poole DJ, et al., Pilot study of vaccination with recombinant CEA-MUC-1-TRICOM poxviral-based vaccines in patients with metastatic carcinoma. Clin Cancer Res, 2008. 14(10): p. 3060-9.GulleyJ.L.ArlenPMTsangKYYokokawaJPalenaCPooleDJet al.Pilot study of vaccination with recombinant CEA-MUC-1-TRICOM poxviral-based vaccines in patients with metastatic carcinomaClin Cancer Res200814103060910.1158/1078-0432.CCR-08-0126267309718483372Search in Google Scholar

de Gruijl, T.D., A.B. Janssen, and V.W. van Beusechem, Arming oncolytic viruses to leverage antitumor immunity. Expert Opin Biol Ther, 2015. 15(7): p. 959-71.de GruijlT.D.JanssenA.B.van BeusechemV.W.Arming oncolytic viruses to leverage antitumor immunityExpert Opin Biol Ther20151579597110.1517/14712598.2015.104443325959450Search in Google Scholar

Lichty, B.D., Breitbach CJ, Stojdl DF, Bell JC., Going viral with cancer immunotherapy. Nat Rev Cancer, 2014. 14(8): p. 559-67.LichtyB.D.BreitbachCJStojdlDFBellJC.Going viral with cancer immunotherapyNat Rev Cancer20141485596710.1038/nrc377024990523Search in Google Scholar

Liu, B.L., Robinson M, Han ZQ, Branston RH, English C, Reay P, et al., ICP34.5 deleted herpes simplex virus with enhanced oncolytic, immune stimulating, and anti-tumour properties. Gene Ther, 2003. 10(4): p. 292-303.LiuB.L.RobinsonMHanZQBranstonRHEnglishCReayPet al.ICP34.5 deleted herpes simplex virus with enhanced oncolytic, immune stimulating, and anti-tumour propertiesGene Ther200310429230310.1038/sj.gt.330188512595888Search in Google Scholar

Andtbacka, R.H., Kaufman HL, Collichio F, Amatruda T, Senzer N, Chesney J, et al., Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma. J Clin Oncol, 2015. 33(25): p. 2780-8.AndtbackaR.H.KaufmanHLCollichioFAmatrudaTSenzerNChesneyJet al.Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced MelanomaJ Clin Oncol201533252780810.1200/JCO.2014.58.337726014293Search in Google Scholar

Rajani, K.R. and R.G. Vile, Harnessing the Power of Onco-Immunotherapy with Checkpoint Inhibitors. Viruses, 2015. 7(11): p. 5889-901.RajaniK.R.VileR.G.Harnessing the Power of Onco-Immunotherapy with Checkpoint InhibitorsViruses2015711588990110.3390/v7112914466498726580645Search in Google Scholar

Wollmann, G., K. Ozduman, and A.N. van den Pol, Oncolytic virus therapy for glioblastoma multiforme: concepts and candidates. Cancer J, 2012. 18(1): p. 69-81.WollmannG.OzdumanK.van den PolA.N.Oncolytic virus therapy for glioblastoma multiforme: concepts and candidatesCancerJ2012181698110.1097/PPO.0b013e31824671c9363233322290260Search in Google Scholar

Baxevanis, C.N., Sotiriadou NN, Gritzapis AD, Sotiropoulou PA, Perez SA, Cacoullos NT, Papamichail M., Immunogenic HER-2/neu peptides as tumor vaccines. Cancer Immunol Immunother, 2006. 55(1): p. 85-95.BaxevanisC.N.SotiriadouNNGritzapisADSotiropoulouPAPerezSACacoullosNTPapamichailM.Immunogenic HER-2/neu peptides as tumor vaccinesCancer Immunol Immunother2006551859510.1007/s00262-005-0692-315948002Search in Google Scholar

Holmes, J.P., Benavides LC, Gates JD, Carmichael MG, Hueman MT, Mittendorf EA, et al., Results of the first phase I clinical trial of the novel II-key hybrid preventive HER-2/neu peptide (AE37) vaccine. J Clin Oncol, 2008. 26(20): p. 3426-33.HolmesJ.P.BenavidesLCGatesJDCarmichaelMGHuemanMTMittendorfEAet al.Results of the first phase I clinical trial of the novel II-key hybrid preventive HER-2/neu peptide (AE37) vaccineJ Clin Oncol2008262034263310.1200/JCO.2007.15.784218612158Search in Google Scholar

Perez, S.A., Anastasopoulou EA, Papamichail M, Baxevanis CN., AE37 peptide vaccination in prostate cancer: identification of biomarkers in the context of prognosis and prediction. Cancer Immunol Immunother, 2014. 63(11): p. 1141-50.PerezS.A.AnastasopoulouEAPapamichailMBaxevanisCN.AE37 peptide vaccination in prostate cancer: identification of biomarkers in the context of prognosis and predictionCancer Immunol Immunother2014631111415010.1007/s00262-014-1582-325052849Search in Google Scholar

Perez, S.A., Anastasopoulou EA, Tzonis P, Gouttefangeas C, Kalbacher H, Papamichail M, Baxevanis CN., AE37 peptide vaccination in prostate cancer: a 4-year immunological assessment updates on a phase I trial. Cancer Immunol Immunother, 2013. 62(10): p. 1599-608.PerezS.A.AnastasopoulouEATzonisPGouttefangeasCKalbacherHPapamichailMBaxevanisCN.AE37 peptide vaccination in prostate cancer: a 4-year immunological assessment updates on a phase I trialCancer Immunol Immunother20136210159960810.1007/s00262-013-1461-323934022Search in Google Scholar

Perez, S.A., Kallinteris NL, Bisias S, Tzonis PK, Georgakopoulou K, Varla-Leftherioti M, et al., Results from a phase I clinical study of the novel Ii-Key/HER-2/neu(776-790) hybrid peptide vaccine in patients with prostate cancer. Clin Cancer Res, 2010. 16(13): p. 3495-506.PerezS.A.KallinterisNLBisiasSTzonisPKGeorgakopoulouKVarla-LeftheriotiMet al.Results from a phase I clinical study of the novel Ii-Key/HER-2/neu(776-790) hybrid peptide vaccine in patients with prostate cancerClin Cancer Res20101613349550610.1158/1078-0432.CCR-10-008520466887Search in Google Scholar

Greene, J., et al., Final pre-specified analysis of the phase II trial of the AE37+GM-CSF vaccine in high risk breast cancer patients to prevent recurrence. J Clin Oncol 2015. 33(_suppl): p. abstr 622.GreeneJ.et al.Final pre-specified analysis of the phase II trial of the AE37+GM-CSF vaccine in high risk breast cancer patients to prevent recurrenceJ Clin Oncol201533_supplp. abstr62210.1200/jco.2015.33.15_suppl.622Search in Google Scholar

Pistamaltzian, N., et al., Preexisting immunity as a potential biomarker for clinical response to AE37 vaccination in breast cancer patients Annals of Oncology, 2015. 26(8_suppl): p. viii1–viii4.PistamaltzianN.et al.Preexisting immunity as a potential biomarker for clinical response to AE37 vaccination in breast cancer patientsAnnals of Oncology201526viii1viii410.1093/annonc/mdv513.07Search in Google Scholar

Sears, A.K., Perez SA, Clifton GT, Benavides LC, Gates JD, Clive KS, et al., AE37: a novel T-cell-eliciting vaccine for breast cancer. Expert Opin Biol Ther, 2011. 11(11): p. 1543-50.SearsA.K.PerezSACliftonGTBenavidesLCGatesJDCliveKSet al.AE37: a novel T-cell-eliciting vaccine for breast cancerExpert Opin Biol Ther2011111115435010.1517/14712598.2011.61688921895539Search in Google Scholar

Twyman-Saint Victor, C.Rech AJ, Maity A, Rengan R, Pauken KE, Stelekati E, et al.: Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature. 2015 Apr 16;520(7547):373-7.Twyman-Saint VictorC.RechAJMaityARenganRPaukenKEStelekatiEet al.Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancerNature2015Apr165207547373710.1038/nature14292440163425754329Search in Google Scholar

Cooper, Z.A., Juneja VR, Sage PT, Frederick DT, Piris A, Mitra D, et al.: Response to BRAF inhibition in melanoma is enhanced when combined with immune checkpoint blockade. Cancer Immunol Res. 2014 Jul; 2(7):643-54.CooperZ.A.JunejaVRSagePTFrederickDTPirisAMitraDet al.Response to BRAF inhibition in melanoma is enhanced when combined with immune checkpoint blockadeCancer Immunol Res2014Jul276435410.1158/2326-6066.CIR-13-0215409712124903021Search in Google Scholar

Crittenden, M.Kohrt H, Levy R, Jones J, Camphausen K, Dicker A, et al.: Current clinical trials testing combinations of immunotherapy and radiation. SeminRadiatOncol. 2015 Jan; 25(1):54-64.CrittendenM.KohrtHLevyRJonesJCamphausenKDickerAet al.Current clinical trials testing combinations of immunotherapy and radiationSeminRadiatOncol2015Jan251546410.1016/j.semradonc.2014.07.003464068725481267Search in Google Scholar

Balachandran, V.P. Cavnar MJ, Zeng S, Bamboat ZM, Ocuin LM, Obaid H, et al.: Imatinib potentiates antitumor T cell responses in gastrointestinal stromal tumor through the inhibition of Ido. Nat Med. 2011 Aug 28; 17(9):1094-100.BalachandranV.P.CavnarMJZengSBamboatZMOcuinLMObaidHet al.Imatinib potentiates antitumor T cell responses in gastrointestinal stromal tumor through the inhibition of IdoNat Med2011Aug28179109410010.1038/nm.2438327827921873989Search in Google Scholar

Hodi FS, Mihm MC, Soiffer RJ, Haluska FG, Butler M, Seiden MV, et al.: Biologic activity of cytotoxic T lymphocyte-associated antigen 4 antibody blockade in previously vaccinated metastatic melanoma and ovarian carcinoma patients. Proc Natl AcadSci U S A (2003) 100(8):4712.HodiFSMihmMCSoifferRJHaluskaFGButlerMSeidenMVet al.Biologic activity of cytotoxic T lymphocyte-associated antigen 4 antibody blockade in previously vaccinated metastatic melanoma and ovarian carcinoma patientsProc Natl AcadSci U S A20031008471210.1073/pnas.083099710015362112682289Search in Google Scholar

Yuan J, Zhou J, Dong Z, Tandon S, Kuk D, Panageas KS, et al.: Pretreatment serum VEGF is associated with clinical response and overall survival in advanced melanoma patients treated with ipilimumab. Cancer Immunol Res (2014) 2(2):127.YuanJZhouJDongZTandonSKukDPanageasKSet al.Pretreatment serum VEGF is associated with clinical response and overall survival in advanced melanoma patients treated with ipilimumabCancer Immunol Res20142212710.1158/2326-6066.CIR-13-0163399110924778276Search in Google Scholar

Zitvogel, L., Kepp, O., & Kroemer, G. Immune parameters affecting the efficacy of chemotherapeutic regimens. Nat Rev ClinOncol. 2011 Mar;8(3):151-60.ZitvogelL.KeppO.KroemerG.Immune parameters affecting the efficacy of chemotherapeutic regimensNat Rev ClinOncol2011Mar831516010.1038/nrclinonc.2010.22321364688Search in Google Scholar

Zitvogel, L., Galluzzi, L., Smyth, M. J., & Kroemer, G. Mechanism of action of conventional and targeted anticancer therapies: Reinstating immunosurveillance. Immunity. 2013 Jul 25; 39(1):74-88.ZitvogelL.GalluzziL.SmythM. J.KroemerG.Mechanism of action of conventional and targeted anticancer therapies: Reinstating immunosurveillanceImmunity2013Jul25391748810.1016/j.immuni.2013.06.01423890065Search in Google Scholar

Zitvogel, L., Tesniere, A., & Kroemer, G. (2006). Cancer despite immunosurveillance: Immunoselection and immunosubversion. Nat Rev Immunol. 2006 Oct; 6(10):715-27.ZitvogelL.TesniereA.KroemerG.2006Cancer despite immunosurveillance: Immunoselection and immunosubversionNat Rev Immunol2006Oct61071527Search in Google Scholar

Robert, C., Thomas, L., Bondarenko, I., O’Day, S., M, D. J., Garbe, C., et al.: Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. 2011 Jun 30; 364(26):2517-26.RobertC.ThomasL.BondarenkoI.O’ DayS.MD. J.GarbeC.et al.Ipilimumab plus dacarbazine for previously untreated metastatic melanomaN Engl J Med2011Jun303642625172610.1056/NEJMoa110462121639810Search in Google Scholar

Reck, M., Bondarenko, I., Luft, A., Serwatowski, P., Barlesi, F., Chacko, R., et al.: Ipilimumab in combination with paclitaxel and carboplatin as first-line therapy inextensive-disease-small-cell lung cancer: Results from a randomized, double-blind, multicenter phase 2 trial. Ann Oncol. 2013 Jan; 24(1):75-83.ReckM.BondarenkoI.LuftA.SerwatowskiP.BarlesiF.ChackoR.et al.Ipilimumab in combination with paclitaxel and carboplatin as first-line therapy inextensive-disease-small-cell lung cancer: Results from a randomized, double-blind, multicenter phase 2 trialAnn Oncol2013Jan241758310.1093/annonc/mds213Search in Google Scholar

Lynch, T. J., Bondarenko, I., Luft, A., Serwatowski, P., Barlesi, F., Chacko, R., et al.: Ipilimumab in combination with paclitaxel and carboplatin as first-line treatment in stage IIIB/IV non-small-cell lung cancer: Results from a randomized, doubleblind, multicenter phase II study. J ClinOncol. 2012 Jun 10; 30(17):2046-54.LynchT. J.BondarenkoI.LuftA.SerwatowskiP.BarlesiF.ChackoR.et al.Ipilimumab in combination with paclitaxel and carboplatin as first-line treatment in stage IIIB/IV non-small-cell lung cancer: Results from a randomized, doubleblind, multicenter phase II studyJ ClinOncol2012Jun10301720465410.1200/JCO.2011.38.4032Search in Google Scholar

Antonia, S. J., Brahmer, J. R., Gettinger, S. N., Chow, L. Q., Juergens, R. A., Shepherd, F. A., et al.: Nivolumab (anti-PD-1; BMS-936558, ONO-4538) in combination with platinum-based doublet chemotherapy (PT-DC) in advanced non-small cell lung cancer(NSCLC). J ClinOncol (2014); 32 (Suppl.; abstr 8113).AntoniaS. J.BrahmerJ. R.GettingerS. N.ChowL. Q.JuergensR. A.ShepherdF. A.et al.Nivolumab (anti-PD-1; BMS-936558, ONO-4538) in combination with platinum-based doublet chemotherapy (PT-DC) in advanced non-small cell lung cancer(NSCLC)J ClinOncol (2014); 32 (Suppl.; abstr 8113)10.1200/jco.2014.32.15_suppl.8113Search in Google Scholar

Curran, M. A., & Allison, J. P.:Tumor vaccines expressing flt3 ligand synergize with ctla-4 blockade to reject pre-implanted tumors. Cancer Res. 2009 Oct 1; 69(19):7747-55.CurranM. A.AllisonJ. P.Tumor vaccines expressing flt3 ligand synergize with ctla-4 blockade to reject pre-implanted tumorsCancer Res2009Oct1691977475510.1158/0008-5472.CAN-08-3289Search in Google Scholar

Le, D. T., Lutz, E., Uram, J. N., Sugar, E. A., Onners, B., Solt, S., et al.: Evaluation of ipilimumab in combination with allogeneic pancreatic tumor cells transfected with a GM-CSF gene in previously treated pancreatic cancer. J Immunother. 2013 Sep; 36(7):382-9.LeD. T.LutzE.UramJ. N.SugarE. A.OnnersB.SoltS.et al.Evaluation of ipilimumab in combination with allogeneic pancreatic tumor cells transfected with a GM-CSF gene in previously treated pancreatic cancerJ Immunother2013Sep367382910.1097/CJI.0b013e31829fb7a2Search in Google Scholar

Gerritsen, W., van den Eertwegh, A. J., de Gruijl, T., van den Berg, H. P., Scheper, R. J., Sacks, N., et al.: Expanded phase I combination trial of GVAX immunotherapy for prostate cancer and ipilimumab in patients with metastatic hormone-refractory prostate cancer (mHPRC). J ClinOncol(2008) 26(Suppl.), 5146.GerritsenW.van den EertweghA. J.de GruijlT.van den BergH. P.ScheperR. J.SacksN.et al.Expanded phase I combination trial of GVAX immunotherapy for prostate cancer and ipilimumab in patients with metastatic hormone-refractory prostate cancer (mHPRC)J ClinOncol(2008)26Suppl514610.1200/jco.2008.26.15_suppl.5146Search in Google Scholar

Espenschied, J., Lamont, J., Longmate, J., Pendas, S., Wang, Z., Diamond, D. J., et al.: CTLA-4 blockade enhances the therapeutic effect of an attenuated poxvirus vaccine targeting p53 in an established murine tumor model. J Immunol. 2003 Mar 15;170(6):3401-7.EspenschiedJ.LamontJ.LongmateJ.PendasS.WangZ.DiamondD. J.et al.CTLA-4 blockade enhances the therapeutic effect of an attenuated poxvirus vaccine targeting p53 in an established murine tumor modelJ Immunol2003Mar1517063401710.4049/jimmunol.170.6.3401Search in Google Scholar

Chakraborty, M., Schlom, J., & Hodge, JW: The combined activation of positive costimulatory signals with modulation of a negative costimulatory signal for the enhancement of vaccine-mediated T-cell responses. Cancer Immunol Immunother. 2007 Sep; 56(9):1471-84.ChakrabortyM.SchlomJ.HodgeJWThe combined activation of positive costimulatory signals with modulation of a negative costimulatory signal for the enhancement of vaccine-mediated T-cell responsesCancer Immunol Immunother2007Sep56914718410.1007/s00262-007-0291-6Search in Google Scholar

Madan, R. A., Mohebtash, M., Arlen, P. M., Vergati, M., Rauckhorst, M., Steinberg, S. M., et al.: Ipilimumab and a poxviral vaccine targeting prostate-specific antigen in metastatic castration-resistant prostate cancer: A phase 1 dose-escalation trial. Lancet Oncol 20102 May; 13(5): 501–508.MadanR. A.MohebtashM.ArlenP. M.VergatiM.RauckhorstM.SteinbergS. M.et al.Ipilimumab and a poxviral vaccine targeting prostate-specific antigen in metastatic castration-resistant prostate cancer: A phase 1 dose-escalation trialLancet Oncol 20102May13550150810.1016/S1470-2045(12)70006-2Search in Google Scholar

eISSN:
1792-362X
Language:
English
Publication timeframe:
4 times per year
Journal Subjects:
Medicine, Clinical Medicine, Internal Medicine, Haematology, Oncology