{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:20:51Z","timestamp":1790767251375,"version":"4.1.0"},"reference-count":150,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,4,16]],"date-time":"2020-04-16T00:00:00Z","timestamp":1586995200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The tumor microenvironment is a complex ecosystem comprised of many different cell types, abnormal vasculature and immunosuppressive cytokines. The irregular growth kinetics with which tumors grow leads to increased oxygen consumption and, in turn, hypoxic conditions. Hypoxia has been associated with poor clinical outcome, increased tumor heterogeneity, emergence of resistant clones and evasion of immune detection. Additionally, hypoxia-driven cell death pathways have traditionally been thought of as tolerogenic processes. However, as researchers working in the field of immunotherapy continue to investigate and unveil new types of immunogenic cell death (ICD), it has become clear that, in some instances, hypoxia may actually induce ICD within a tumor. In this review, we will discuss hypoxia-driven immune escape that drives poor prognostic outcomes, the ability of hypoxia to induce ICD and potential therapeutic targets amongst hypoxia pathways.<\/jats:p>","DOI":"10.3390\/cells9040992","type":"journal-article","created":{"date-parts":[[2020,4,16]],"date-time":"2020-04-16T13:01:39Z","timestamp":1587042099000},"page":"992","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":271,"title":["Hypoxia-Driven Immune Escape in the Tumor Microenvironment"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2197-4395","authenticated-orcid":false,"given":"Alyssa","family":"Vito","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Biomedical Sciences, McMaster Immunology Research Centre, McMaster University, Hamilton, ON L8S 4K1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nader","family":"El-Sayes","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biomedical Sciences, McMaster Immunology Research Centre, McMaster University, Hamilton, ON L8S 4K1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1725-5873","authenticated-orcid":false,"given":"Karen","family":"Mossman","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, ON L8S 4K1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/978-3-030-34461-0_18","article-title":"Hypoxia compromises anti-cancer immune responses","volume":"1232","author":"Multhoff","year":"2020","journal-title":"Advances in Experimental Medicine and Biology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1177\/1947601911423654","article-title":"Hypoxia-Induced Angiogenesis: Good and Evil","volume":"2","author":"Krock","year":"2011","journal-title":"Genes Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"849","DOI":"10.3858\/emm.2009.41.12.103","article-title":"Hypoxia and angiogenesis: Regulation of hypoxia-inducible factors via novel binding factors","volume":"41","author":"Chen","year":"2009","journal-title":"Exp. Mol. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1158\/2326-6066.CIR-16-0129-T","article-title":"RIG-I Resists Hypoxia-Induced Immunosuppression and Dedifferentiation","volume":"5","author":"Engel","year":"2017","journal-title":"Cancer Immunol. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2250","DOI":"10.18632\/oncotarget.2948","article-title":"Inhibition of HIF-1\u03b1 by PX-478 enhances the anti-tumor effect of gemcitabine by inducing immunogenic cell death in pancreatic ductal adenocarcinoma","volume":"6","author":"Zhao","year":"2015","journal-title":"Oncotarget"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/978-3-030-12734-3_8","article-title":"Mechanistic justifications of systemic therapeutic oxygenation of tumors to weaken the hypoxia inducible factor 1\u03b1-mediated immunosuppression","volume":"1136","author":"Hatfield","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_7","first-page":"6269","article-title":"Hypoxia induces immunogenic cell death of cancer cells by enhancing the exposure of cell surface calreticulin in an endoplasmic reticulum stress-dependent manner","volume":"18","author":"Han","year":"2019","journal-title":"Oncol. Lett."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1007\/s12032-019-1329-2","article-title":"The role of vascular endothelial growth factor in the hypoxic and immunosuppressive tumor microenvironment: Perspectives for therapeutic implications","volume":"37","author":"Tamura","year":"2020","journal-title":"Med. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"40","DOI":"10.3389\/fimmu.2018.00040","article-title":"Hypoxia pathway proteins as central mediators of metabolism in the tumor cells and their microenvironment","volume":"9","author":"Sormendi","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.tibs.2012.06.004","article-title":"Passing the baton: The HIF switch","volume":"37","author":"Koh","year":"2012","journal-title":"Trends Biochem. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.ccr.2006.08.026","article-title":"Recruitment of HIF-1\u03b1 and HIF-2\u03b1 to common target genes is differentially regulated in neuroblastoma: HIF-2\u03b1 promotes an aggressive phenotype","volume":"10","author":"Fredlund","year":"2006","journal-title":"Cancer Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"8386","DOI":"10.1073\/pnas.140087397","article-title":"The transcription factor EPAS-1\/hypoxia-inducible factor 2\u03b1 plays an important role in vascular remodeling","volume":"97","author":"Peng","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"525","DOI":"10.3748\/wjg.v10.i4.525","article-title":"Expression of HIF-2\u03b1\/EPAS1 in hepatocellular carcinoma","volume":"10","author":"Bangoura","year":"2004","journal-title":"World J. Gastroenterol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.7554\/eLife.03342","article-title":"Quantitative determinants of aerobic glycolysis identify flux through the enzyme GAPDH as a limiting step","volume":"3","author":"Shestov","year":"2014","journal-title":"Elife"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.cmet.2007.10.002","article-title":"The Biology of Cancer: Metabolic Reprogramming Fuels Cell Growth and Proliferation","volume":"7","author":"DeBerardinis","year":"2008","journal-title":"Cell Metab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1126\/science.1193494","article-title":"The control of the metabolic switch in cancers by oncogenes and tumor suppressor genes","volume":"330","author":"Levine","year":"2010","journal-title":"Science"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/nrc2981","article-title":"Regulation of cancer cell metabolism","volume":"11","author":"Cairns","year":"2011","journal-title":"Nat. Rev. Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/nrc3038","article-title":"Otto Warburg\u2019s contributions to current concepts of cancer metabolism","volume":"11","author":"Koppenol","year":"2011","journal-title":"Nat. Rev. Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Wielockx, B., and Meneses, A. (2016). PHD2: From hypoxia regulation to disease progression. Hypoxia, 53.","DOI":"10.2147\/HP.S53576"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"11800","DOI":"10.1074\/jbc.M116.713941","article-title":"Hypercapnia suppresses the HIF-dependent adaptive response to hypoxia","volume":"291","author":"Selfridge","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"343","DOI":"10.2174\/1566524018666181109121849","article-title":"Role of HIF-1 in Cancer Progression: Novel Insights. A Review","volume":"18","author":"Pezzuto","year":"2018","journal-title":"Curr. Mol. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1189\/jlb.0208082","article-title":"Human dendritic cells differentiated in hypoxia down-modulate antigen uptake and change their chemokine expression profile","volume":"84","author":"Elia","year":"2008","journal-title":"J. Leukoc. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3723","DOI":"10.1182\/blood-2008-02-142091","article-title":"Divergent effects of hypoxia on dendritic cell functions","volume":"112","author":"Mancino","year":"2008","journal-title":"Blood"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/nri.2016.107","article-title":"Immunogenic cell death in cancer and infectious disease","volume":"17","author":"Galluzzi","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.it.2015.02.004","article-title":"Macrophages and cancer: From mechanisms to therapeutic implications","volume":"36","author":"Ostuni","year":"2015","journal-title":"Trends Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1172\/JCI59643","article-title":"Macrophage plasticity and polarization: In vivo veritas","volume":"122","author":"Sica","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3672","DOI":"10.1172\/JCI84427","article-title":"The impact of hypoxia on tumor-associated macrophages","volume":"126","author":"Henze","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3479","DOI":"10.1158\/0008-5472.CAN-14-3587","article-title":"Perivascular M2 macrophages stimulate tumor relapse after chemotherapy","volume":"75","author":"Hughes","year":"2015","journal-title":"Cancer Res."},{"key":"ref_29","first-page":"3335","article-title":"Correlation of histological localization of tumor-associated macrophages with clinicopathological features in endometrial cancer","volume":"24","author":"Ohno","year":"2004","journal-title":"Anticancer Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"137","DOI":"10.2215\/CJN.09430915","article-title":"B cells, antibodies, and more","volume":"11","author":"Hoffman","year":"2016","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1146\/annurev-immunol-020711-074934","article-title":"Immune Regulatory Function of B Cells","volume":"30","author":"Mauri","year":"2012","journal-title":"Annu. Rev. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Krzywinska, E., and Stockmann, C. (2018). Hypoxia, metabolism and immune cell function. Biomedicines, 6.","DOI":"10.3390\/biomedicines6020056"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2170","DOI":"10.1073\/pnas.052706699","article-title":"Abnormal B lymphocyte development and autoimmunity in hypoxia-inducible factor 1\u03b1-deficient chimeric mice","volume":"99","author":"Kojima","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1128\/MCB.23.1.359-369.2003","article-title":"Hypoxia-Inducible Factor 1 Is Essential for Cell Cycle Arrest during Hypoxia","volume":"23","author":"Goda","year":"2003","journal-title":"Mol. Cell. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Meng, X., Gr\u00f6tsch, B., Luo, Y., Knaup, K.X., Wiesener, M.S., Chen, X.X., Jantsch, J., Fillatreau, S., Schett, G., and Bozec, A. (2018). Hypoxia-inducible factor-1\u03b1 is a critical transcription factor for IL-10-producing B cells in autoimmune disease. Nat. Commun., 9.","DOI":"10.1038\/s41467-017-02683-x"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/imr.12396","article-title":"Regulation of germinal center B-cell differentiation","volume":"270","author":"Zhang","year":"2016","journal-title":"Immunol. Rev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1038\/ni.3664","article-title":"Gsk3 is a metabolic checkpoint regulator in B cells","volume":"18","author":"Jellusova","year":"2017","journal-title":"Nat. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3626","DOI":"10.4049\/jimmunol.1302062","article-title":"Metabolic Reprogramming Is Required for Antibody Production That Is Suppressed in Anergic but Exaggerated in Chronically BAFF-Exposed B Cells","volume":"192","author":"Wang","year":"2014","journal-title":"J. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Griss, J., Bauer, W., Wagner, C., Simon, M., Chen, M., Grabmeier-Pfistershammer, K., Maurer-Granofszky, M., Roka, F., Penz, T., and Bock, C. (2019). B cells sustain inflammation and predict response to immune checkpoint blockade in human melanoma. Nat. Commun., 10.","DOI":"10.1038\/s41467-019-12160-2"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1038\/nri3442","article-title":"The integration of T cell migration, differentiation and function","volume":"13","author":"Masopust","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"8975","DOI":"10.1073\/pnas.1811702116","article-title":"Hypoxia-inducible factors in CD4+ T cells promote metabolism, switch cytokine secretion, and T cell help in humoral immunity","volume":"116","author":"Cho","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"C580","DOI":"10.1152\/ajpcell.00204.2015","article-title":"Hypoxia-inducible factors in T lymphocyte differentiation and function. A review in the theme: Cellular responses to hypoxia","volume":"309","author":"Tao","year":"2015","journal-title":"Am. J. Physiol. - Cell Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1111\/j.1600-065X.2012.01152.x","article-title":"mTOR, metabolism, and the regulation of T-cell differentiation and function","volume":"249","author":"Waickman","year":"2012","journal-title":"Immunol. Rev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4661","DOI":"10.4049\/jimmunol.172.8.4661","article-title":"Regulation of T Lymphocyte Metabolism","volume":"172","author":"Frauwirth","year":"2004","journal-title":"J. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Chen, J.L.Y., Lucas, J.E., Schroeder, T., Mori, S., Wu, J., Nevins, J., Dewhirst, M., West, M., and Chi, J.T. (2008). The genomic analysis of lactic acidosis and acidosis response in human cancers. PLoS Genet., 4.","DOI":"10.1371\/journal.pgen.1000293"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.it.2015.02.008","article-title":"Overcoming T cell exhaustion in infection and cancer","volume":"36","author":"Pauken","year":"2015","journal-title":"Trends Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"6140","DOI":"10.4049\/jimmunol.167.11.6140","article-title":"Differential Effects of Physiologically Relevant Hypoxic Conditions on T Lymphocyte Development and Effector Functions","volume":"167","author":"Caldwell","year":"2001","journal-title":"J. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4479","DOI":"10.1172\/JCI69589","article-title":"Inhibiting glycolytic metabolism enhances CD8+ T cell memory and antitumor function","volume":"123","author":"Sukumar","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Parodi, M., Raggi, F., Cangelosi, D., Manzini, C., Balsamo, M., Blengio, F., Eva, A., Varesio, L., Pietra, G., and Moretta, L. (2018). Hypoxia modifies the transcriptome of human NK cells, modulates their immunoregulatory profile, and influences NK cell subset migration. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.02358"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2756","DOI":"10.1002\/eji.201343448","article-title":"Hypoxia downregulates the expression of activating receptors involved in NK-cell-mediated target cell killing without affecting ADCC","volume":"43","author":"Balsamo","year":"2013","journal-title":"Eur. J. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Krzywinska, E., Kantari-Mimoun, C., Kerdiles, Y., Sobecki, M., Isagawa, T., Gotthardt, D., Castells, M., Haubold, J., Millien, C., and Viel, T. (2017). Loss of HIF-1\u03b1 in natural killer cells inhibits tumour growth by stimulating non-productive angiogenesis. Nat. Commun., 8.","DOI":"10.1038\/s41467-017-01599-w"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"194.37","DOI":"10.4049\/jimmunol.202.Supp.194.37","article-title":"Hypoxia-Inducible Factor-1\u03b1 is upregulated in Natural Killer cells by Interleukin-2 and hypoxia via PI3K\/mTOR signaling pathway","volume":"202","author":"Cluff","year":"2019","journal-title":"J. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1038\/nri2506","article-title":"Myeloid-derived suppressor cells as regulators of the immune system","volume":"9","author":"Gabrilovich","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1038\/nrc2444","article-title":"The role of myeloid cells in the promotion of tumour angiogenesis","volume":"8","author":"Murdoch","year":"2008","journal-title":"Nat. Rev. Cancer"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2439","DOI":"10.1084\/jem.20100587","article-title":"HIF-1\u03b1 regulates function and differentiation of myeloid-derived suppressor cells in the tumor microenvironment","volume":"207","author":"Corzo","year":"2010","journal-title":"J. Exp. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/S1673-8527(09)60061-8","article-title":"Contribution of myeloid-derived suppressor cells to tumor-induced immune suppression, angiogenesis, invasion and metastasis","volume":"37","author":"Ye","year":"2010","journal-title":"J. Genet. Genomics"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-017-00530-7","article-title":"Hypoxia inducible factor HIF-1 promotes myeloid-derived suppressor cells accumulation through ENTPD2\/CD39L1 in hepatocellular carcinoma","volume":"8","author":"Chiu","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1002\/hep.28655","article-title":"Hypoxia induces myeloid-derived suppressor cell recruitment to hepatocellular carcinoma through chemokine (C-C motif) ligand 26","volume":"64","author":"Chiu","year":"2016","journal-title":"Hepatology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1038\/nature04695","article-title":"Lysyl oxidase is essential for hypoxia-induced metastasis","volume":"440","author":"Erler","year":"2006","journal-title":"Nature"},{"key":"ref_60","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_61","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/cdd.2011.96","article-title":"Molecular definitions of cell death subroutines: Recommendations of the Nomenclature Committee on Cell Death 2012","volume":"19","author":"Galluzzi","year":"2012","journal-title":"Cell Death Differ."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"151","DOI":"10.4161\/auto.5338","article-title":"Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes","volume":"4","author":"Klionsky","year":"2008","journal-title":"Autophagy"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1038\/nrm2952","article-title":"Mitochondria and cell death: Outer membrane permeabilization and beyond","volume":"11","author":"Tait","year":"2010","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_64","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_65","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_66","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1084\/jem.20050915","article-title":"Caspase-dependent immunogenicity of doxorubicin-induced tumor cell death","volume":"202","author":"Casares","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_67","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_68","doi-asserted-by":"crossref","first-page":"4854","DOI":"10.1111\/jcmm.14356","article-title":"Immunogenic cell death in cancer therapy: Present and emerging inducers","volume":"23","author":"Zhou","year":"2019","journal-title":"J. Cell. Mol. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"4800","DOI":"10.1158\/1078-0432.CCR-10-1572","article-title":"Superior efficacy of tumor cell vaccines grown in physiologic oxygen","volume":"16","author":"Olin","year":"2010","journal-title":"Clin. Cancer Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"6583","DOI":"10.1158\/0008-5472.CAN-11-1166","article-title":"Oxygen is a master regulator of the immunogenicity of primary human glioma cells","volume":"71","author":"Olin","year":"2011","journal-title":"Cancer Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1038\/emboj.2011.497","article-title":"A novel pathway combining calreticulin exposure and ATP secretion in immunogenic cancer cell death","volume":"31","author":"Garg","year":"2012","journal-title":"EMBO J."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/s00262-011-1184-2","article-title":"Hypericin-based photodynamic therapy induces surface exposure of damage-associated molecular patterns like HSP70 and calreticulin","volume":"61","author":"Garg","year":"2012","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1038\/emboj.2012.2","article-title":"Enlightening the impact of immunogenic cell death in photodynamic cancer therapy","volume":"31","author":"Galluzzi","year":"2012","journal-title":"EMBO J."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1990","DOI":"10.1021\/cr5004198","article-title":"Nanoparticles in photodynamic therapy","volume":"115","author":"Lucky","year":"2015","journal-title":"Chem. Rev."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1038\/onc.2016.225","article-title":"Hypoxic stress: Obstacles and opportunities for innovative immunotherapy of cancer","volume":"36","author":"Chouaib","year":"2017","journal-title":"Oncogene"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"8633","DOI":"10.1021\/acsnano.8b04371","article-title":"Bioinspired hybrid protein oxygen nanocarrier amplified photodynamic therapy for eliciting anti-tumor immunity and abscopal effect","volume":"12","author":"Chen","year":"2018","journal-title":"ACS Nano"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e966","DOI":"10.1038\/cddis.2013.493","article-title":"Strange attractors: DAMPs and autophagy link tumor cell death and immunity","volume":"4","author":"Hou","year":"2013","journal-title":"Cell Death Dis."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e826","DOI":"10.1038\/cddis.2013.372","article-title":"Calreticulin surface exposure is abrogated in cells lacking, chaperone-mediated autophagy-essential gene, LAMP2A","volume":"4","author":"Garg","year":"2013","journal-title":"Cell Death Dis."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1038\/cdd.2008.84","article-title":"Hypoxia signals autophagy in tumor cells via AMPK activity, independent of HIF-1, BNIP3, and BNIP3L","volume":"15","author":"Papandreou","year":"2008","journal-title":"Cell Death Differ."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2570","DOI":"10.1128\/MCB.00166-09","article-title":"Hypoxia-Induced Autophagy Is Mediated through Hypoxia-Inducible Factor Induction of BNIP3 and BNIP3L via Their BH3 Domains","volume":"29","author":"Bellot","year":"2009","journal-title":"Mol. Cell. Biol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"35803","DOI":"10.1074\/jbc.M705231200","article-title":"Bnip3 mediates the hypoxia-induced inhibition on mammalian target of rapamycin by interacting with Rheb","volume":"282","author":"Li","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.molcel.2010.10.030","article-title":"mTORC1 signaling under hypoxic conditions is controlled by atm-dependent phosphorylation of HIF-1\u03b1","volume":"40","author":"Cam","year":"2010","journal-title":"Mol. Cell"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"80842","DOI":"10.18632\/oncotarget.13099","article-title":"Late-stage inhibition of autophagy enhances calreticulin surface exposure","volume":"7","author":"Li","year":"2016","journal-title":"Oncotarget"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.cell.2017.01.017","article-title":"Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy","volume":"168","author":"Sharma","year":"2017","journal-title":"Cell"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.coi.2015.12.007","article-title":"The urgent need to recover MHC class I in cancers for effective immunotherapy","volume":"39","author":"Garrido","year":"2016","journal-title":"Curr. Opin. Immunol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/S0065-230X(01)83005-0","article-title":"MHC antigens and tumor escape from immune surveillance","volume":"83","author":"Garrido","year":"2001","journal-title":"Adv. Cancer Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1006\/scbi.2001.0404","article-title":"HLA class I antigen abnormalities and immune escape by malignant cells","volume":"12","author":"Seliger","year":"2002","journal-title":"Semin. Cancer Biol."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Sethumadhavan, S., Silva, M., Philbrook, P., Nguyen, T., Hatfield, S.M., Ohta, A., and Sitkovsky, M.V. (2017). Hypoxia and hypoxia-inducible factor (HIF) downregulate antigen-presenting MHC class I molecules limiting tumor cell recognition by T cells. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0187314"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"149","DOI":"10.4049\/immunohorizons.1900017","article-title":"Intratumoral Hypoxia Reduces IFN-\u03b3\u2013Mediated Immunity and MHC Class I Induction in a Preclinical Tumor Model","volume":"3","author":"Murthy","year":"2019","journal-title":"ImmunoHorizons"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"4746","DOI":"10.1158\/0008-5472.CAN-08-0054","article-title":"Hypoxia increases tumor cell shedding of MHC class I chain-related molecule: Role of nitric oxide","volume":"68","author":"Siemens","year":"2008","journal-title":"Cancer Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1186\/s40425-019-0627-8","article-title":"Metabolic stress in cancer cells induces immune escape through a PI3K-dependent blockade of IFN\u03b3receptor signaling","volume":"7","author":"Marijt","year":"2019","journal-title":"J. Immunother. Cancer"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"152","DOI":"10.3389\/fimmu.2019.02298","article-title":"The Diverse Function of PD-1\/PD-L Pathway Beyond Cancer","volume":"10","author":"Qin","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"S1063","DOI":"10.4103\/0973-1482.202891","article-title":"Expression of programmed death-ligand 1 and hypoxia-inducible factor-1\u03b1 proteins in endometrial carcinoma","volume":"14","author":"Tawadros","year":"2018","journal-title":"J. Cancer Res. Ther."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1084\/jem.20131916","article-title":"PD-L1 is a novel direct target of HIF-1\u03b1, and its blockade under hypoxia enhanced: MDSC-mediated T cell activation","volume":"211","author":"Noman","year":"2014","journal-title":"J. Exp. Med."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Cubillos-Zapata, C., Avenda\u00f1o-Ortiz, J., Hernandez-Jimenez, E., Toledano, V., Casas-Martin, J., Varela-Serrano, A., Torres, M., Almendros, I., Casitas, R., and Fern\u00e1ndez-Navarro, I. (2017). Hypoxia-induced PD-L1\/PD-1 crosstalk impairs T-cell function in sleep apnoea. Eur. Respir. J., 50.","DOI":"10.1183\/13993003.00833-2017"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12943-018-0928-4","article-title":"Role of the tumor microenvironment in PD-L1\/PD-1-mediated tumor immune escape","volume":"18","author":"Jiang","year":"2019","journal-title":"Mol. Cancer"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.eururo.2015.11.029","article-title":"Renal Cell Carcinoma Programmed Death-ligand 1, a New Direct Target of Hypoxia-inducible Factor-2 Alpha, is Regulated by von Hippel\u2013Lindau Gene Mutation Status","volume":"70","author":"Messai","year":"2016","journal-title":"Eur. Urol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1046\/j.1365-2567.2000.00121.x","article-title":"CD28, CTLA-4 and their ligands: Who does what and to whom?","volume":"101","author":"Sansom","year":"2000","journal-title":"Immunology"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1182\/blood-2017-06-741033","article-title":"CTLA-4: A moving target in immunotherapy","volume":"131","author":"Rowshanravan","year":"2018","journal-title":"Blood"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1002\/eji.201142053","article-title":"Influence of hypoxia-inducible factor 1\u03b1 on dendritic cell differentiation and migration","volume":"42","author":"Reizis","year":"2012","journal-title":"Eur. J. Immunol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1016\/j.cell.2015.08.012","article-title":"Phosphoenolpyruvate Is a Metabolic Checkpoint of Anti-tumor T Cell Responses","volume":"162","author":"Ho","year":"2015","journal-title":"Cell"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1016\/j.cell.2015.08.016","article-title":"Metabolic competition in the tumor microenvironment is a driver of cancer progression Graphical Abstract HHS Public Access","volume":"162","author":"Chang","year":"2015","journal-title":"Cell"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"175","DOI":"10.3389\/fimmu.2017.00175","article-title":"Antigen Loss Variants: Catching Hold of Escaping Foes","volume":"8","author":"Vyas","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1016\/j.cell.2018.03.041","article-title":"Chemoresistance Evolution in Triple-Negative Breast Cancer Delineated by Single-Cell Sequencing","volume":"173","author":"Kim","year":"2018","journal-title":"Cell"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/nature18945","article-title":"Neoantigen landscape dynamics during human melanoma\u2013T cell interactions","volume":"536","author":"Verdegaal","year":"2016","journal-title":"Nature"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2009","DOI":"10.1158\/0008-5472.CAN-04-3216","article-title":"Potent Selection of Antigen Loss Variants of B16 Melanoma following Inflammatory Killing of Melanocytes In vivo","volume":"65","author":"Kottke","year":"2005","journal-title":"Cancer Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"2052","DOI":"10.1634\/stemcells.2007-1016","article-title":"Hypoxia Causes Downregulation of Mismatch Repair System and Genomic Instability in Stem Cells","volume":"26","year":"2008","journal-title":"Stem Cells"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Cowman, S., Pizer, B., and See, V. (2020). Downregulation of both mismatch repair and non-homologous end-joining pathways in hypoxic brain tumour cell lines. bioRxiv Cancer Biol.","DOI":"10.1101\/2020.01.15.907584"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"3265","DOI":"10.1128\/MCB.23.9.3265-3273.2003","article-title":"Decreased Expression of the DNA Mismatch Repair Gene Mlh1 under Hypoxic Stress in Mammalian Cells","volume":"23","author":"Mihaylova","year":"2003","journal-title":"Mol. Cell. Biol."},{"key":"ref_110","first-page":"7603","article-title":"Hypoxia-induced enrichment and mutagenesis of cells that have lost DNA mismatch repair","volume":"61","author":"Kondo","year":"2001","journal-title":"Cancer Res."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/2041-9414-4-5","article-title":"Tumor hypoxia as a driving force in genetic instability","volume":"4","author":"Luoto","year":"2013","journal-title":"Genome Integr."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1242\/jcs.092262","article-title":"Chronic hypoxia compromises repair of DNA double-strand breaks to drive genetic instability","volume":"125","author":"Kumareswaran","year":"2012","journal-title":"J. Cell Sci."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1631\/jzus.B1400221","article-title":"feng Hypoxia-inducible factor 1 and breast cancer metastasis","volume":"16","author":"Liu","year":"2015","journal-title":"J. Zhejiang Univ. Sci. B"},{"key":"ref_114","first-page":"399","article-title":"HIF-1\u03b1 contributes to hypoxia-induced invasion and metastasis of esophageal carcinoma via inibiting E-cadherin and promoting MMP-2 expression","volume":"66","author":"Jing","year":"2012","journal-title":"Acta Med. Okayama"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1053\/sonc.2002.37263","article-title":"Role of angiogenesis in tumor growth and metastasis","volume":"29","author":"Folkman","year":"2002","journal-title":"Semin. Oncol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1097\/PPO.0000000000000138","article-title":"The Contribution of Angiogenesis to the Process of Metastasis","volume":"21","author":"Bielenberg","year":"2015","journal-title":"Cancer J. (USA)"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1097\/00006676-200301000-00010","article-title":"Hypoxia-inducible factor 1 regulates vascular endothelial growth factor expression in human pancreatic cancer","volume":"26","author":"Reber","year":"2003","journal-title":"Pancreas"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1002\/cncr.10774","article-title":"Association of hypoxia-inducible factors 1\u03b1 and 2\u03b1 with activated angiogenic pathways and prognosis in patients with endometrial carcinoma","volume":"95","author":"Sivridis","year":"2002","journal-title":"Cancer"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"13264","DOI":"10.1073\/pnas.1101321108","article-title":"VEGF is essential for hypoxia-inducible factor-mediated neovascularization but dispensable for endothelial sprouting","volume":"108","author":"Oladipupo","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"45643","DOI":"10.1074\/jbc.M404097200","article-title":"Vascular endothelial growth factor transcriptional activation is mediated by hypoxia-inducible factor 1\u03b1, HDM2, and p70S6K1 in response to phosphatidylinositol 3-kinase\/AKT signaling","volume":"279","author":"Skinner","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"R64","DOI":"10.1186\/bcr3458","article-title":"HIF-1\u03b1\/GPER signaling mediates the expression of VEGF induced by hypoxia in breast cancer associated fibroblasts (CAFs)","volume":"15","author":"Lappano","year":"2013","journal-title":"Breast Cancer Res."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1159\/000491806","article-title":"Association between Hypoxia-Inducible Factor-2\u03b1 (HIF-2\u03b1) Expression and Colorectal Cancer and Its Prognostic Role: A Systematic Analysis","volume":"48","author":"Han","year":"2018","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_123","first-page":"371","article-title":"Prognostic significance of VHL, HIF1A, HIF2A, VEGFA and p53 expression in patients with clear-cell renal cell carcinoma treated with sunitinib as first-line treatment","volume":"55","author":"Wierzbicki","year":"2019","journal-title":"Int. J. Oncol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"2292","DOI":"10.2353\/ajpath.2010.090972","article-title":"HIF1A overexpression is associated with poor prognosis in a cohort of 731 colorectal cancers","volume":"176","author":"Baba","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"553","DOI":"10.4155\/fmc.13.17","article-title":"Hypoxia inducible factor pathway inhibitors as anticancer therapeutics","volume":"5","author":"Burroughs","year":"2013","journal-title":"Future Med. Chem."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.pharmthera.2016.04.009","article-title":"Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer","volume":"164","author":"Wigerup","year":"2016","journal-title":"Pharmacol. Ther."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"2780","DOI":"10.1111\/j.1582-4934.2009.00876.x","article-title":"Development of HIF-1 inhibitors for cancer therapy","volume":"13","author":"Onnis","year":"2009","journal-title":"J. Cell. Mol. Med."},{"key":"ref_128","first-page":"1","article-title":"Hypoxia-driven immunosuppressive metabolites in the tumor microenvironment: New approaches for combinational immunotherapy","volume":"9","author":"Li","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"489","DOI":"10.3349\/ymj.2017.58.3.489","article-title":"Development of Inhibitors Targeting Hypoxia-Inducible Factor 1 and 2 for Cancer Therapy","volume":"58","author":"Yu","year":"2017","journal-title":"Yonsei Med. J."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11912-019-0752-z","article-title":"HIF Inhibitors: Status of Current Clinical Development","volume":"21","author":"Fallah","year":"2019","journal-title":"Curr. Oncol. Rep."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/bjc.2013.285","article-title":"Inhibition of VEGF expression through blockade of Hif1\u03b1 and STAT3 signalling mediates the anti-angiogenic effect of melatonin in HepG2 liver cancer cells","volume":"109","author":"Benet","year":"2013","journal-title":"Br. J. Cancer"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"e2843","DOI":"10.1038\/cddis.2017.235","article-title":"The novel hypoxia-inducible factor-1\u03b1 inhibitor IDF-11774 regulates cancer metabolism, thereby suppressing tumor growth","volume":"8","author":"Ban","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"3995","DOI":"10.1128\/MCB.21.12.3995-4004.2001","article-title":"HER2 (neu) Signaling Increases the Rate of Hypoxia-Inducible Factor 1 (HIF-1) Synthesis: Novel Mechanism for HIF-1-Mediated Vascular Endothelial Growth Factor Expression","volume":"21","author":"Laughner","year":"2001","journal-title":"Mol. Cell. Biol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/S1535-6108(03)00187-9","article-title":"TSC2 regulates VEGF through mTOR-dependent and -independent pathways","volume":"4","author":"Brugarolas","year":"2003","journal-title":"Cancer Cell"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"7004","DOI":"10.1128\/MCB.22.20.7004-7014.2002","article-title":"Regulation of Hypoxia-Inducible Factor 1 Expression and Function by the Mammalian Target of Rapamycin","volume":"22","author":"Hudson","year":"2002","journal-title":"Mol. Cell. Biol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1158\/0008-5472.CAN-14-3362","article-title":"Control of PD-L1 expression by oncogenic activation of the AKT-mTOR pathway in non-small cell lung cancer","volume":"76","author":"Lastwika","year":"2016","journal-title":"Cancer Res."},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Song, M., Chen, D., Lu, B., Wang, C., Zhang, J., Huang, L., Wang, X., Timmons, C.L., Hu, J., and Liu, B. (2013). PTEN Loss Increases PD-L1 Protein Expression and Affects the Correlation between PD-L1 Expression and Clinical Parameters in Colorectal Cancer. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0065821"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.2147\/OTT.S130481","article-title":"A blockade of PD-L1 produced antitumor and antimetastatic effects in an orthotopic mouse pancreatic cancer model via the PI3K\/Akt\/mTOR signaling pathway","volume":"10","author":"Zhao","year":"2017","journal-title":"Onco. Targets. Ther."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1158\/2326-6066.CIR-13-0127","article-title":"PD-L1 expression in triple-negative breast cancer","volume":"2","author":"Mittendorf","year":"2014","journal-title":"Cancer Immunol. Res."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1186\/s40425-019-0812-9","article-title":"Blocking CD47 efficiently potentiated therapeutic effects of anti-angiogenic therapy in non-small cell lung cancer","volume":"7","author":"Zhang","year":"2019","journal-title":"J. Immunother. Cancer"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"17561","DOI":"10.1073\/pnas.1215397109","article-title":"Vascular normalizing doses of antiangiogenic treatment reprogram the immunosuppressive tumor microenvironment and enhance immunotherapy","volume":"109","author":"Huang","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1038\/mt.2008.232","article-title":"Hypoxia enhances the replication of oncolytic herpes simplex virus","volume":"17","author":"Aghi","year":"2009","journal-title":"Mol. Ther."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.surg.2004.04.016","article-title":"Employing tumor hypoxia to enhance oncolytic viral therapy in breast cancer","volume":"136","author":"Pin","year":"2004","journal-title":"Surgery"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"71","DOI":"10.2147\/VAAT.S17832","article-title":"The impact of hypoxia on oncolytic virotherapy","volume":"3","author":"Guo","year":"2011","journal-title":"Virus Adapt. Treat."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1182\/blood.V100.3.1084","article-title":"Rapamycin inhibits macropinocytosis and mannose receptor-mediated endocytosis by bone marrow-derived dendritic cells","volume":"100","author":"Hackstein","year":"2002","journal-title":"Blood"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"4457","DOI":"10.1182\/blood-2002-11-3370","article-title":"Rapamycin inhibits IL-4-induced dendritic cell maturation in vitro and dendritic cell mobilization and function in vivo","volume":"101","author":"Hackstein","year":"2003","journal-title":"Blood"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1038\/nri2546","article-title":"Immunoregulatory functions of mTOR inhibition","volume":"9","author":"Thomson","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"3279","DOI":"10.1158\/0008-5472.CAN-15-0454","article-title":"Rapamycin impairs antitumor CD8p T-cell responses and vaccine-induced tumor eradication","volume":"75","author":"Chaoul","year":"2015","journal-title":"Cancer Res."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"4743","DOI":"10.1182\/blood-2004-10-3932","article-title":"Rapamycin selectively expands CD4+CD25+FoxP3 + regulatory T cells","volume":"105","author":"Battaglia","year":"2005","journal-title":"Blood"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"8338","DOI":"10.4049\/jimmunol.177.12.8338","article-title":"Rapamycin Promotes Expansion of Functional CD4 + CD25 + FOXP3 + Regulatory T Cells of Both Healthy Subjects and Type 1 Diabetic Patients","volume":"177","author":"Battaglia","year":"2006","journal-title":"J. Immunol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/4\/992\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:31:21Z","timestamp":1760362281000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/4\/992"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,16]]},"references-count":150,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2020,4]]}},"alternative-id":["cells9040992"],"URL":"https:\/\/doi.org\/10.3390\/cells9040992","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,16]]}}}