{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:54:46Z","timestamp":1790834086621,"version":"4.1.0"},"reference-count":70,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2020,9,16]],"date-time":"2020-09-16T00:00:00Z","timestamp":1600214400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per la Ricerca sul Cancro","doi-asserted-by":"publisher","award":["2017 IG20654"],"award-info":[{"award-number":["2017 IG20654"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012100","name":"Associazione Italiana Contro le Leucemie-Linfomi e Mieloma","doi-asserted-by":"publisher","award":["Bologna section"],"award-info":[{"award-number":["Bologna section"]}],"id":[{"id":"10.13039\/501100012100","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Foundation Corrado and Bruno Maria Zaini-Bologna","award":["Foundation Corrado and Bruno Maria Zaini-Bologna"],"award-info":[{"award-number":["Foundation Corrado and Bruno Maria Zaini-Bologna"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Background: Recent evidence demonstrated that the treatment of acute myeloid leukemia (AML) cells with daunorubicin (DNR) but not cytarabine (Ara-C) results in immunogenic cell death (ICD). In the clinical setting, chemotherapy including anthracyclines and Ara-C remains a gold standard for AML treatment. In the last decade, etoposide (Eto) and fludarabine (Flu) have been added to the standard treatment for AML to potentiate its therapeutic effect and have been tested in many trials. Very little data are available about the ability of these drugs to induce ICD. Methods: AML cells were treated with all four drugs. Calreticulin and heat shock protein 70\/90 translocation, non-histone chromatin-binding protein high mobility group box 1 and adenosine triphosphate release were evaluated. The treated cells were pulsed into dendritic cells (DCs) and used for in vitro immunological tests. Results: Flu and Ara-C had no capacity to induce ICD-related events. Interestingly, Eto was comparable to DNR in inducing all ICD events, resulting in DC maturation. Moreover, Flu was significantly more potent in inducing suppressive T regulatory cells compared to other drugs. Conclusions: Our results indicate a novel and until now poorly investigated feature of antineoplastic drugs commonly used for AML treatment, based on their different immunogenic potential.<\/jats:p>","DOI":"10.3390\/ijms21186802","type":"journal-article","created":{"date-parts":[[2020,9,16]],"date-time":"2020-09-16T20:44:13Z","timestamp":1600289053000},"page":"6802","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["A Screening of Antineoplastic Drugs for Acute Myeloid Leukemia Reveals Contrasting Immunogenic Effects of Etoposide and Fludarabine"],"prefix":"10.3390","volume":"21","author":[{"given":"Darina","family":"Ocadlikova","sequence":"first","affiliation":[{"name":"Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Istituto di Ematologia \u201cSer\u00e0gnoli\u201d, Universit\u00e0 degli Studi, 40138 Bologna, Italy"},{"name":"Azienda Ospedaliero-Universitaria di Bologna, via Albertoni 15, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6618-6694","authenticated-orcid":false,"given":"Clara","family":"Iannarone","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Istituto di Ematologia \u201cSer\u00e0gnoli\u201d, Universit\u00e0 degli Studi, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1332-2792","authenticated-orcid":false,"given":"Anna Rita","family":"Redavid","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Istituto di Ematologia \u201cSer\u00e0gnoli\u201d, Universit\u00e0 degli Studi, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Cavo","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Istituto di Ematologia \u201cSer\u00e0gnoli\u201d, Universit\u00e0 degli Studi, 40138 Bologna, Italy"},{"name":"Azienda Ospedaliero-Universitaria di Bologna, via Albertoni 15, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Curti","sequence":"additional","affiliation":[{"name":"Azienda Ospedaliero-Universitaria di Bologna, via Albertoni 15, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.3389\/fimmu.2017.01918","article-title":"ATP Release from Chemotherapy-Treated Dying Leukemia Cells Elicits an Immune Suppressive Effect by Increasing Regulatory T Cells and Tolerogenic Dendritic Cells","volume":"8","author":"Lecciso","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4821","DOI":"10.1158\/0008-5472.CAN-11-0950","article-title":"Human tumor cells killed by anthracyclines induce a tumor-specific immune response","volume":"71","author":"Fucikova","year":"2011","journal-title":"Cancer Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3113","DOI":"10.1182\/blood-2016-08-731737","article-title":"Calreticulin exposure by malignant blasts correlates with robust anticancer immunity and improved clinical outcome in AML patients","volume":"128","author":"Fucikova","year":"2016","journal-title":"Blood"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e104","DOI":"10.1038\/cddis.2010.82","article-title":"Calreticulin exposure on malignant blasts predicts a cellular anticancer immune response in patients with acute myeloid leukemia","volume":"1","author":"Wemeau","year":"2010","journal-title":"Cell Death Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1146\/annurev-immunol-032712-100008","article-title":"Immunogenic cell death in cancer therapy","volume":"31","author":"Kroemer","year":"2013","journal-title":"Annu. Rev. Immunol."},{"key":"ref_6","first-page":"1549","article-title":"Immunogenic apoptosis in human acute myeloid leukemia (AML): Primary human AML cells expose calreticulin and release heat shock protein (HSP) 70 and HSP90 during apoptosis","volume":"25","author":"Fredly","year":"2011","journal-title":"Oncol. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4839","DOI":"10.1182\/blood-2006-10-054221","article-title":"Bortezomib enhances dendritic cell (DC)-mediated induction of immunity to human myeloma via exposure of cell surface heat shock protein 90 on dying tumor cells: Therapeutic implications","volume":"109","author":"Spisek","year":"2007","journal-title":"Blood"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1038\/cdd.2013.48","article-title":"Danger signalling during cancer cell death: Origins, plasticity and regulation","volume":"21","author":"Garg","year":"2014","journal-title":"Cell Death Differ."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1038\/nm1622","article-title":"Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy","volume":"13","author":"Apetoh","year":"2007","journal-title":"Nat. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1126\/science.1208347","article-title":"Autophagy-dependent anticancer immune responses induced by chemotherapeutic agents in mice","volume":"334","author":"Michaud","year":"2011","journal-title":"Science"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/nm1523","article-title":"Calreticulin exposure dictates the immunogenicity of cancer cell death","volume":"13","author":"Obeid","year":"2007","journal-title":"Nat. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1002\/biof.1125","article-title":"Cancer immunogenicity, danger signals, and DAMPs: What, when, and how?","volume":"39","author":"Garg","year":"2013","journal-title":"Biofactors"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1038\/nm.2028","article-title":"Activation of the NLRP3 inflammasome in dendritic cells induces IL-1beta-dependent adaptive immunity against tumors","volume":"15","author":"Ghiringhelli","year":"2009","journal-title":"Nat. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1038\/nm.3708","article-title":"Cancer cell-autonomous contribution of type I interferon signaling to the efficacy of chemotherapy","volume":"20","author":"Sistigu","year":"2014","journal-title":"Nat. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1111\/j.1600-065X.2007.00567.x","article-title":"Ecto-calreticulin in immunogenic chemotherapy","volume":"220","author":"Obeid","year":"2007","journal-title":"Immunol. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1111\/j.1600-065X.2007.00573.x","article-title":"The interaction between HMGB1 and TLR4 dictates the outcome of anticancer chemotherapy and radiotherapy","volume":"220","author":"Apetoh","year":"2007","journal-title":"Immunol. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e24568","DOI":"10.4161\/onci.24568","article-title":"ATP-dependent recruitment, survival and differentiation of dendritic cell precursors in the tumor bed after anticancer chemotherapy","volume":"2","author":"Ma","year":"2013","journal-title":"Oncoimmunology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1038\/nature08296","article-title":"Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance","volume":"461","author":"Elliott","year":"2009","journal-title":"Nature"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.4161\/onci.20428","article-title":"Activation of dendritic cells by tumor cell death","volume":"1","author":"Cirone","year":"2012","journal-title":"Oncoimmunology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/nrc3380","article-title":"Immunogenic cell death and DAMPs in cancer therapy","volume":"12","author":"Krysko","year":"2012","journal-title":"Nat. Rev. Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e1278332","DOI":"10.1080\/2162402X.2016.1278332","article-title":"Calreticulin promotes immunity and type I interferon-dependent survival in mice with acute myeloid leukemia","volume":"6","author":"Chen","year":"2017","journal-title":"Oncoimmunology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.imlet.2017.11.006","article-title":"Relevance of the chaperone-like protein calreticulin for the biological behavior and clinical outcome of cancer","volume":"193","author":"Fucikova","year":"2018","journal-title":"Immunol. Lett."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1158\/2159-8290.CD-16-0313","article-title":"Efficacy and Biological Correlates of Response in a Phase II Study of Venetoclax Monotherapy in Patients with Acute Myelogenous Leukemia","volume":"6","author":"Konopleva","year":"2016","journal-title":"Cancer Discov."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1080\/17474086.2018.1459184","article-title":"Checkpoint inhibitors and acute myelogenous leukemia: Promises and challenges","volume":"11","author":"Alfayez","year":"2018","journal-title":"Expert Rev. Hematol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1111\/bjh.15078","article-title":"Immune checkpoint molecules in acute myeloid leukaemia: Managing the double-edged sword","volume":"181","author":"Hobo","year":"2018","journal-title":"Br. J. Haematol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1678","DOI":"10.1200\/JCO.2016.70.6374","article-title":"Idarubicin Dose Escalation during Consolidation Therapy for Adult Acute Myeloid Leukemia","volume":"35","author":"Bradstock","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3878","DOI":"10.1182\/blood-2015-01-623447","article-title":"A randomized comparison of daunorubicin 90 mg\/m2 vs 60 mg\/m2 in AML induction: Results from the UK NCRI AML17 trial in 1206 patients","volume":"125","author":"Burnett","year":"2015","journal-title":"Blood"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e253","DOI":"10.1016\/S1470-2045(17)30277-2","article-title":"Escalated anthracycline dose in adult AML","volume":"18","author":"Balakrishnan","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1182\/blood-2017-04-777722","article-title":"Cytarabine dose in the consolidation treatment of AML: A systematic review and meta-analysis","volume":"130","author":"Magina","year":"2017","journal-title":"Blood"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1080\/14656566.2017.1391216","article-title":"Cytarabine and daunorubicin for the treatment of acute myeloid leukemia","volume":"18","author":"Murphy","year":"2017","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1182\/blood-2016-08-733196","article-title":"Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel","volume":"129","author":"Estey","year":"2017","journal-title":"Blood"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1002\/ajh.24439","article-title":"Acute myeloid leukemia: 2016 Update on risk-stratification and management","volume":"91","author":"Estey","year":"2016","journal-title":"Am. J. Hematol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1200\/JCO.2010.30.1820","article-title":"Therapeutic advances in acute myeloid leukemia","volume":"29","author":"Burnett","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1182\/blood-2015-08-604520","article-title":"An update of current treatments for adult acute myeloid leukemia","volume":"127","author":"Dombret","year":"2016","journal-title":"Blood"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/10428194.2019.1620943","article-title":"FLAI induction regimen in elderly patients with acute myeloid leukemia","volume":"60","author":"Cerrano","year":"2019","journal-title":"Leuk. Lymphoma"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1002\/ajh.23337","article-title":"Fludarabine, cytarabine, and attenuated-dose idarubicin (m-FLAI) combination therapy for elderly acute myeloid leukemia patients","volume":"88","author":"Kim","year":"2013","journal-title":"Am. J. Hematol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"41600","DOI":"10.18632\/oncotarget.6113","article-title":"Concepts and mechanisms underlying chemotherapy induced immunogenic cell death: Impact on clinical studies and considerations for combined therapies","volume":"6","author":"Gebremeskel","year":"2015","journal-title":"Oncotarget"},{"key":"ref_38","first-page":"275","article-title":"Corrigendum: \u201cCombinatorial Strategies for the Induction of Immunogenic Cell Death\u201d","volume":"6","author":"Bezu","year":"2015","journal-title":"Front. Immunol."},{"key":"ref_39","unstructured":"Jung, K.-H., Paik, J.-Y., Park, J., Quach, C., Lee, E.J., Choe, Y.S., and Lee, K.-H. (2011, January 12\u201316). Targeting of calreticulin exposure for optical imaging of etoposide-induced immunogenic tumor cell death. Proceedings of the Molecular Targets and Cancer Therapeutics, San Francisco, CA, USA."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1038\/cdd.2016.5","article-title":"Immunogenic versus tolerogenic phagocytosis during anticancer therapy: Mechanisms and clinical translation","volume":"23","author":"Garg","year":"2016","journal-title":"Cell Death Differ."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1016\/j.ccell.2015.10.012","article-title":"Immunological Effects of Conventional Chemotherapy and Targeted Anticancer Agents","volume":"28","author":"Galluzzi","year":"2015","journal-title":"Cancer Cell"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Knaus, H.A., Berglund, S., Hackl, H., Blackford, A.L., Zeidner, J.F., Montiel-Esparza, R., Mukhopadhyay, R., Vanura, K., Blazar, B.R., and Karp, J.E. (2018). Signatures of CD8+ T cell dysfunction in AML patients and their reversibility with response to chemotherapy. JCI Insight, 3.","DOI":"10.1172\/jci.insight.120974"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/978-3-319-67577-0_5","article-title":"Immunogenic and Non-immunogenic Cell Death in the Tumor Microenvironment","volume":"1036","author":"Pitt","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.3389\/fonc.2019.01004","article-title":"Chemotherapy-Induced Tumor Cell Death at the Crossroads Between Immunogenicity and Immunotolerance: Focus on Acute Myeloid Leukemia","volume":"9","author":"Ocadlikova","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"34330","DOI":"10.1038\/srep34330","article-title":"Etoposide Induces Apoptosis in Activated Human Hepatic Stellate Cells via ER Stress","volume":"6","author":"Wang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1038\/s41418-017-0044-9","article-title":"eIF2\u03b1 phosphorylation is pathognomonic for immunogenic cell death","volume":"25","author":"Bezu","year":"2018","journal-title":"Cell Death Differ."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1038\/emboj.2009.1","article-title":"Mechanisms of pre-apoptotic calreticulin exposure in immunogenic cell death","volume":"28","author":"Panaretakis","year":"2009","journal-title":"EMBO J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"20071","DOI":"10.1073\/pnas.1206360109","article-title":"Combination of glycolysis inhibition with chemotherapy results in an antitumor immune response","volume":"109","author":"Zunino","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1038\/s41435-018-0047-7","article-title":"Ecto-Calreticulin is essential for an efficient immunogenic cell death stimulation in mouse melanoma","volume":"20","author":"Giglio","year":"2019","journal-title":"Genes Immun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e955691","DOI":"10.4161\/21624011.2014.955691","article-title":"Consensus guidelines for the detection of immunogenic cell death","volume":"3","author":"Kepp","year":"2014","journal-title":"Oncoimmunology"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Davidson-Moncada, J., Viboch, E., Church, S.E., Warren, S.E., and Rutella, S. (2018). Dissecting the Immune Landscape of Acute Myeloid Leukemia. Biomedicines, 6.","DOI":"10.3390\/biomedicines6040110"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1002\/cncr.31896","article-title":"The distribution of T-cell subsets and the expression of immune checkpoint receptors and ligands in patients with newly diagnosed and relapsed acute myeloid leukemia","volume":"125","author":"Williams","year":"2019","journal-title":"Cancer"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Vadakekolathu, J., Minden, M.D., Hood, T., Church, S.E., Reeder, S., Altmann, H., Sullivan, A.H., Viboch, E.J., Patel, T., and Ibrahimova, N. (2020). Immune landscapes predict chemotherapy resistance and immunotherapy response in acute myeloid leukemia. Sci. Transl. Med., 12.","DOI":"10.1126\/scitranslmed.aaz0463"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2022","DOI":"10.3324\/haematol.2010.025924","article-title":"Indoleamine 2,3-dioxygenase-expressing leukemic dendritic cells impair a leukemia-specific immune response by inducing potent T regulatory cells","volume":"95","author":"Curti","year":"2010","journal-title":"Haematologica"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1007\/s12185-013-1436-3","article-title":"Clinical significance of Treg cell frequency in acute myeloid leukemia","volume":"98","author":"Yang","year":"2013","journal-title":"Int. J. Hematol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1182\/blood-2010-04-277939","article-title":"Early lymphocyte recovery after intensive timed sequential chemotherapy for acute myelogenous leukemia: Peripheral oligoclonal expansion of regulatory T cells","volume":"117","author":"Kanakry","year":"2011","journal-title":"Blood"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3325","DOI":"10.1158\/1078-0432.CCR-08-3010","article-title":"Increased frequency and suppression by regulatory T cells in patients with acute myelogenous leukemia","volume":"15","author":"Szczepanski","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.3389\/fimmu.2018.01274","article-title":"Increased Regulatory T Cells in Peripheral Blood of Acute Myeloid Leukemia Patients Rely on Tumor Necrosis Factor (TNF)-\u03b1-TNF Receptor-2 Pathway","volume":"9","author":"Wang","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1182\/bloodadvances.2019000792","article-title":"Immune profiles in acute myeloid leukemia bone marrow associate with patient age, T-cell receptor clonality, and survival","volume":"4","author":"Dufva","year":"2020","journal-title":"Blood Adv."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1002\/ijc.25791","article-title":"Elevated frequencies of CD4+ CD25+ CD127lo regulatory T cells is associated to poor prognosis in patients with acute myeloid leukemia","volume":"129","author":"Zhang","year":"2011","journal-title":"Int. J. Cancer"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/978-3-319-67577-0_7","article-title":"Chemo-Immunotherapy: Role of Indoleamine 2,3-Dioxygenase in Defining Immunogenic Versus Tolerogenic Cell Death in the Tumor Microenvironment","volume":"1036","author":"Johnson","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2262","DOI":"10.3109\/10428194.2011.607527","article-title":"Treatment of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue with fludarabine: Effect on tumor microenvironment","volume":"52","author":"Raderer","year":"2011","journal-title":"Leuk. Lymphoma"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.cellimm.2012.07.001","article-title":"Tumor-infiltrating regulatory T cells delineated by upregulation of PD-1 and inhibitory receptors","volume":"278","author":"Park","year":"2012","journal-title":"Cell Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1111\/j.1600-065X.2010.00923.x","article-title":"The PD-1 pathway in tolerance and autoimmunity","volume":"236","author":"Francisco","year":"2010","journal-title":"Immunol. Rev."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1038\/nature04444","article-title":"Restoring function in exhausted CD8 T cells during chronic viral infection","volume":"439","author":"Barber","year":"2006","journal-title":"Nature"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1002\/cncr.24899","article-title":"Tumor cell expression of programmed cell death-1 ligand 1 is a prognostic factor for malignant melanoma","volume":"116","author":"Hino","year":"2010","journal-title":"Cancer"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/nri2343","article-title":"How regulatory T cells work","volume":"8","author":"Vignali","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1007\/s00412-010-0286-5","article-title":"Nuclear reformation after mitosis requires downregulation of the Ran GTPase effector RanBP1 in mammalian cells","volume":"119","author":"Ciciarello","year":"2010","journal-title":"Chromosoma"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"253191","DOI":"10.1155\/2015\/253191","article-title":"PGE2-induced IDO1 inhibits the capacity of fully mature DCs to elicit an in vitro antileukemic immune response","volume":"2015","author":"Trabanelli","year":"2015","journal-title":"J. Immunol. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1016\/j.exphem.2005.08.005","article-title":"Interleukin-12 production by leukemia-derived dendritic cells counteracts the inhibitory effect of leukemic microenvironment on T cells","volume":"33","author":"Curti","year":"2005","journal-title":"Exp. Hematol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/18\/6802\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:10:39Z","timestamp":1760177439000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/18\/6802"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,16]]},"references-count":70,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2020,9]]}},"alternative-id":["ijms21186802"],"URL":"https:\/\/doi.org\/10.3390\/ijms21186802","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,16]]}}}