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Review Article

指导缺氧肿瘤微环境和 HIF 阐明癌症免疫疗法在药物靶点方面的现有前景和挑战

卷 23, 期 5, 2022

发表于: 01 March, 2022

页: [471 - 485] 页: 15

弟呕挨: 10.2174/1389450123666220111114649

价格: $65

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摘要

癌症现在也被反映为肿瘤微环境的疾病，主要被认为是一种失控的遗传和细胞表达疾病。在过去的二十年里，在认识肿瘤微环境的动态及其对影响对各种抗癌疗法和药物的反应的贡献方面取得了重大而迅速的进展。肿瘤微环境的调节和免疫检查点阻断在癌症免疫治疗和药物靶点中很有趣。同时，可以通过调节免疫调节通路来实施免疫治疗策略；然而，肿瘤微环境通过其显着的异质性在抑制抗肿瘤免疫方面发挥着重要作用。缺氧诱导因子 (HIF) 是实体瘤异质性的重要贡献者，也是肿瘤微环境中驱动适应以防止免疫监视的关键压力源。这里的检查点抑制剂会阻止癌细胞阻止免疫系统激活的能力，进而放大人体的免疫系统以帮助破坏癌细胞。这些抑制剂影响的常见检查点是 PD-1/PDL1 和 CTLA-4 通路，涉及的重要药物主要是 Ipilimumab 和 Nivolumab，以及该组中的其他药物。针对缺氧肿瘤微环境可能提供一种新的免疫治疗策略，打破传统的癌症治疗耐药性，构建个性化精准医疗和癌症药物靶点的框架。我们希望这些知识能够深入了解靶向缺氧的治疗潜力，并帮助开发新的抗癌药物组合方法，以提高现有癌症疗法（包括免疫疗法）的有效性。

关键词: 肿瘤微环境、缺氧、HIF、免疫治疗、检查点抑制剂、免疫监测、精准医疗。

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[1]
Zhang Y, Zhang Z. The history and advances in cancer immunotherapy: understanding the characteristics of tumor-infiltrating immune cells and their therapeutic implications. Cell Mol Immunol 2020; 17(8): 807-21.
[http://dx.doi.org/10.1038/s41423-020-0488-6] [PMID: 32612154]
[2]
Petrova V, Annicchiarico-Petruzzelli M, Melino G, Amelio I. The hypoxic tumour microenvironment. Oncogenesis 2018; 7(1): 10.
[http://dx.doi.org/10.1038/s41389-017-0011-9] [PMID: 29362402]
[3]
Jing X, Yang F, Shao C, et al. Role of hypoxia in cancer therapy by regulating the tumor microenvironment. Mol Cancer 2019; 18(1): 157.
[http://dx.doi.org/10.1186/s12943-019-1089-9] [PMID: 31711497]
[4]
Vito A, El-Sayes N, Mossman K. Hypoxia-driven immune escape in the tumor microenvironment. Cells 2020; 9(4): 992.
[http://dx.doi.org/10.3390/cells9040992] [PMID: 32316260]
[5]
Jun JC, Rathore A, Younas H, Gilkes D, Polotsky VY. Hypoxia-inducible factors and cancer. Curr Sleep Med Rep 2017; 3(1): 1-10.
[http://dx.doi.org/10.1007/s40675-017-0062-7] [PMID: 28944164]
[6]
Krock BL, Skuli N, Simon MC. Hypoxia-induced angiogenesis: good and evil. Genes Cancer 2011; 2(12): 1117-33.
[http://dx.doi.org/10.1177/1947601911423654] [PMID: 22866203]
[7]
Qin Y, Roszik J, Chattopadhyay C, et al. Hypoxia-driven mechanism of vemurafenib resistance in melanoma. Mol Cancer Ther 2016; 15(10): 2442-54.
[http://dx.doi.org/10.1158/1535-7163.MCT-15-0963] [PMID: 27458138]
[8]
Jiang L, Greenwood TR, Artemov D, et al. Localized hypoxia results in spatially heterogeneous metabolic signatures in breast tumor models. Neoplasia 2012; 14(8): 732-41.
[http://dx.doi.org/10.1593/neo.12858] [PMID: 22952426]
[9]
Al Tameemi W, Dale TP, Al-Jumaily RMK, Forsyth NR. Hypoxia-modified cancer cell metabolism. Front Cell Dev Biol 2019; 7: 4.
[http://dx.doi.org/10.3389/fcell.2019.00004] [PMID: 30761299]
[10]
Vaupel P, Mayer A. Hypoxia in cancer: significance and impact on clinical outcome. Cancer Metastasis Rev 2007; 26(2): 225-39.
[http://dx.doi.org/10.1007/s10555-007-9055-1] [PMID: 17440684]
[11]
Graham K, Unger E. Overcoming tumor hypoxia as a barrier to radiotherapy, chemotherapy and immunotherapy in cancer treatment. Int J Nanomedicine 2018; 13: 6049-58.
[http://dx.doi.org/10.2147/IJN.S140462] [PMID: 30323592]
[12]
Casazza A, Di Conza G, Wenes M, Finisguerra V, Deschoemaeker S, Mazzone M. Tumor stroma: a complexity dictated by the hypoxic tumor microenvironment. Oncogene 2014; 33(14): 1743-54.
[http://dx.doi.org/10.1038/onc.2013.121] [PMID: 23604130]
[13]
Schito L. Bridging angiogenesis and immune evasion in the hypoxic tumor microenvironment. Am J Physiol Regul Integr Comp Physiol 2018; 315(6): R1072-84.
[http://dx.doi.org/10.1152/ajpregu.00209.2018] [PMID: 30183339]
[14]
Chen L, Endler A, Shibasaki F. Hypoxia and angiogenesis: regulation of hypoxia-inducible factors via novel binding factors. Exp Mol Med 2009; 41(12): 849-57.
[http://dx.doi.org/10.3858/emm.2009.41.12.103] [PMID: 19942820]
[15]
Engel C, Brügmann G, Lambing S, et al. RIG-I Resists hypoxia-induced immunosuppression and dedifferentiation. Cancer Immunol Res 2017; 5(6): 455-67.
[http://dx.doi.org/10.1158/2326-6066.CIR-16-0129-T] [PMID: 28468914]
[16]
Zhao T, Ren H, Jia L, et al. Inhibition of HIF-1α by PX-478 enhances the anti-tumor effect of gemcitabine by inducing immunogenic cell death in pancreatic ductal adenocarcinoma. Oncotarget 2015; 6(4): 2250-62.
[http://dx.doi.org/10.18632/oncotarget.2948] [PMID: 25544770]
[17]
Hatfield S, Veszeleiova K, Steingold J, Sethuraman J, Sitkovsky M. Mechanistic justifications of systemic therapeutic oxygenation of tumors to weaken the hypoxia inducible factor 1-mediated immunosuppression. Adv Exp Med Biol 2019; 1136: 113-21.
[http://dx.doi.org/10.1007/978-3-030-12734-3_8] [PMID: 31201720]
[18]
Han YK, Park GY, Bae MJI, Kim JS, Jo WS, Lee CG. Hypoxia induces immunogenic cell death of cancer cells by enhancing the exposure of cell surface calreticulin in an endoplasmic reticulum stress-dependent manner. Oncol Lett 2019; 18(6): 6269-74.
[http://dx.doi.org/10.3892/ol.2019.10986] [PMID: 31788104]
[19]
Postow MA, Callahan MK, Wolchok JD. Immune checkpoint blockade in cancer therapy. J Clin Oncol 2015; 33(17): 1974-82.
[http://dx.doi.org/10.1200/JCO.2014.59.4358] [PMID: 25605845]
[20]
Skrombolas D, Frelinger JG. Challenges and developing solutions for increasing the benefits of IL-2 treatment in tumor therapy. Expert Rev Clin Immunol 2014; 10(2): 207-17.
[http://dx.doi.org/10.1586/1744666X.2014.875856] [PMID: 24410537]
[21]
Dine J, Gordon R, Shames Y, Kasler MK, Barton-Burke M. Immune checkpoint inhibitors: an innovation in immunotherapy for the treatment and management of patients with cancer. Asia Pac J Oncol Nurs 2017; 4(2): 127-35.
[http://dx.doi.org/10.4103/apjon.apjon_4_17] [PMID: 28503645]
[22]
Darvin P, Toor SM, Sasidharan Nair V, Elkord E. Immune checkpoint inhibitors: recent progress and potential biomarkers. Exp Mol Med 2018; 50(12): 1-11.
[http://dx.doi.org/10.1038/s12276-018-0191-1] [PMID: 30546008]
[23]
Ventola CL. Cancer immunotherapy, part 1: current strategies and agents. P&T 2017; 42(6): 375-83.
[PMID: 28579724]
[24]
Semenza GL. Hypoxia-inducible factors in physiology and medicine. Cell 2012; 148(3): 399-408.
[http://dx.doi.org/10.1016/j.cell.2012.01.021] [PMID: 22304911]
[25]
Shay JE, Celeste Simon M. Hypoxia-inducible factors: crosstalk between inflammation and metabolism. Semin Cell Dev Biol 2012; 23(4): 389-94.
[http://dx.doi.org/10.1016/j.semcdb.2012.04.004] [PMID: 22525300]
[26]
Noman MZ, Hasmim M, Messai Y, et al. Hypoxia: a key player in antitumor immune response. a review in the theme: cellular responses to hypoxia. Am J Physiol Cell Physiol 2015; 309(9): C569-79.
[http://dx.doi.org/10.1152/ajpcell.00207.2015] [PMID: 26310815]
[27]
Mennerich D, Kubaichuk K, Kietzmann T. DUBs, hypoxia, and cancer. Trends Cancer 2019; 5(10): 632-53.
[http://dx.doi.org/10.1016/j.trecan.2019.08.005] [PMID: 31706510]
[28]
Okumura F, Joo-Okumura A, Nakatsukasa K, Kamura T. Hypoxia-inducible factor-2α stabilizes the von Hippel-Lindau (VHL) disease suppressor, Myb-related protein 2. PLoS One 2017; 12(4): e0175593.
[http://dx.doi.org/10.1371/journal.pone.0175593] [PMID: 28394947]
[29]
Palazon A, Goldrath AW, Nizet V, Johnson RS. HIF transcription factors, inflammation, and immunity. Immunity 2014; 41(4): 518-28.
[http://dx.doi.org/10.1016/j.immuni.2014.09.008] [PMID: 25367569]
[30]
Jin X, Dai L, Ma Y, Wang J, Liu Z. Implications of HIF-1α in the tumorigenesis and progression of pancreatic cancer. Cancer Cell Int 2020; 20: 273.
[http://dx.doi.org/10.1186/s12935-020-01370-0] [PMID: 32587480]
[31]
Loh CY, Chai JY, Tang TF, et al. The E-cadherin and n-cadherin switch in epithelial-to-mesenchymal transition: signaling, therapeutic implications, and challenges. Cells 2019; 8(10): 1118.
[http://dx.doi.org/10.3390/cells8101118] [PMID: 31547193]
[32]
Song Y, Ye M, Zhou J, Wang ZW, Zhu X. Restoring e-cadherin expression by natural compounds for anticancer therapies in genital and urinary cancers. Mol Ther Oncolytics 2019; 14: 130-8.
[http://dx.doi.org/10.1016/j.omto.2019.04.005] [PMID: 31194121]
[33]
Bruner HC, Derksen PWB. Loss of e-cadherin-dependent cell-cell adhesion and the development and progression of cancer. Cold Spring Harb Perspect Biol 2018; 10(3): a029330.
[http://dx.doi.org/10.1101/cshperspect.a029330] [PMID: 28507022]
[34]
Vadde R, Vemula S, Jinka R, Merchant N, Bramhachari PV, Nagaraju GP. Role of hypoxia-inducible factors (HIF) in the maintenance of stemness and malignancy of colorectal cancer. Crit Rev Oncol Hematol 2017; 113: 22-7.
[http://dx.doi.org/10.1016/j.critrevonc.2017.02.025] [PMID: 28427511]
[35]
Schito L, Semenza GL. Hypoxia-inducible factors: master regulators of cancer progression. Trends Cancer 2016; 2(12): 758-70.
[http://dx.doi.org/10.1016/j.trecan.2016.10.016] [PMID: 28741521]
[36]
Yang Z, Guo J, Weng L, Tang W, Jin S, Ma W. Myeloid-derived suppressor cells-new and exciting players in lung cancer. J Hematol Oncol 2020; 13(1): 10.
[http://dx.doi.org/10.1186/s13045-020-0843-1] [PMID: 32005273]
[37]
Hatziioannou A, Alissafi T, Verginis P. Myeloid-derived suppressor cells and T regulatory cells in tumors: unraveling the dark side of the force. J Leukoc Biol 2017; 102(2): 407-21.
[http://dx.doi.org/10.1189/jlb.5VMR1116-493R] [PMID: 28360184]
[38]
Cha YJ, Koo JS. Role of tumor-associated myeloid cells in breast cancer. Cells 2020; 9(8): 1785.
[http://dx.doi.org/10.3390/cells9081785] [PMID: 32726950]
[39]
Corzo CA, Condamine T, Lu L, et al. HIF-1α regulates function and differentiation of myeloid-derived suppressor cells in the tumor microenvironment. J Exp Med 2010; 207(11): 2439-53.
[http://dx.doi.org/10.1084/jem.20100587] [PMID: 20876310]
[40]
Li Y, Patel SP, Roszik J, Qin Y. Hypoxia-driven immunosuppressive metabolites in the tumor microenvironment: new approaches for combinational immunotherapy. Front Immunol 2018; 9: 1591.
[http://dx.doi.org/10.3389/fimmu.2018.01591] [PMID: 30061885]
[41]
Wen Q, Han T, Wang Z, Jiang S. Role and mechanism of programmed death-ligand 1 in hypoxia-induced liver cancer immune escape. Oncol Lett 2020; 19(4): 2595-601.
[http://dx.doi.org/10.3892/ol.2020.11369] [PMID: 32218809]
[42]
Huang CY, Ye ZH, Huang MY, Lu JJ. Regulation of CD47 expression in cancer cells. Transl Oncol 2020; 13(12): 100862.
[http://dx.doi.org/10.1016/j.tranon.2020.100862] [PMID: 32920329]
[43]
Noman MZ, Messai Y, Carré T, et al. Microenvironmental hypoxia orchestrating the cell stroma cross talk, tumor progression and antitumor response. Crit Rev Immunol 2011; 31(5): 357-77.
[http://dx.doi.org/10.1615/CritRevImmunol.v31.i5.10] [PMID: 22142164]
[44]
Gabrilovich DI, Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 2009; 9(3): 162-74.
[http://dx.doi.org/10.1038/nri2506] [PMID: 19197294]
[45]
Pinto ML, Rios E, Durães C, et al. The two faces of tumor-associated macrophages and their clinical significance in colorectal cancer. Front Immunol 2019; 10: 1875.
[http://dx.doi.org/10.3389/fimmu.2019.01875] [PMID: 31481956]
[46]
Räihä MR, Puolakkainen PA. Tumor-associated macrophages (TAMs) as biomarkers for gastric cancer: A review. Chronic Dis Transl Med 2018; 4(3): 156-63.
[PMID: 30276362]
[47]
Scodeller P, Simón-Gracia L, Kopanchuk S, et al. Precision targeting of tumor macrophages with a cd206 binding peptide. Sci Rep 2017; 7(1): 14655.
[http://dx.doi.org/10.1038/s41598-017-14709-x] [PMID: 29116108]
[48]
Xu ZJ, Gu Y, Wang CZ, et al. The M2 macrophage marker CD206: a novel prognostic indicator for acute myeloid leukemia. OncoImmunology 2019; 9(1): 1683347.
[http://dx.doi.org/10.1080/2162402X.2019.1683347] [PMID: 32002295]
[49]
Lin Y, Xu J, Lan H. Tumor-associated macrophages in tumor metastasis: biological roles and clinical therapeutic applications. J Hematol Oncol 2019; 12(1): 76.
[http://dx.doi.org/10.1186/s13045-019-0760-3] [PMID: 31300030]
[50]
Silva VL, Al-Jamal WT. Exploiting the cancer niche: Tumor-associated macrophages and hypoxia as promising synergistic targets for nano-based therapy. J Control Release 2017; 253: 82-96.
[http://dx.doi.org/10.1016/j.jconrel.2017.03.013] [PMID: 28285930]
[51]
Laitala A, Erler JT. Hypoxic signalling in tumour stroma. Front Oncol 2018; 8: 189.
[http://dx.doi.org/10.3389/fonc.2018.00189] [PMID: 29896451]
[52]
Jiang X, Wang J, Deng X, et al. The role of microenvironment in tumor angiogenesis. J Exp Clin Cancer Res 2020; 39(1): 204.
[http://dx.doi.org/10.1186/s13046-020-01709-5] [PMID: 32993787]
[53]
Quintero-Fabián S, Arreola R, Becerril-Villanueva E, et al. Role of matrix metalloproteinases in angiogenesis and cancer. Front Oncol 2019; 9: 1370.
[http://dx.doi.org/10.3389/fonc.2019.01370] [PMID: 31921634]
[54]
Ayob AZ, Ramasamy TS. Cancer stem cells as key drivers of tumour progression. J Biomed Sci 2018; 25(1): 20.
[http://dx.doi.org/10.1186/s12929-018-0426-4] [PMID: 29506506]
[55]
Keith B, Simon MC. Hypoxia-inducible factors, stem cells, and cancer. Cell 2007; 129(3): 465-72.
[http://dx.doi.org/10.1016/j.cell.2007.04.019] [PMID: 17482542]
[56]
Dongre A, Weinberg RA. New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer. Nat Rev Mol Cell Biol 2019; 20(2): 69-84.
[http://dx.doi.org/10.1038/s41580-018-0080-4] [PMID: 30459476]
[57]
Qian J, Rankin EB. Hypoxia-induced phenotypes that mediate tumor heterogeneity. Adv Exp Med Biol 2019; 1136: 43-55.
[http://dx.doi.org/10.1007/978-3-030-12734-3_3] [PMID: 31201715]
[58]
Hasmim M, Noman MZ, Lauriol J, et al. Hypoxia-dependent inhibition of tumor cell susceptibility to CTL-mediated lysis involves NANOG induction in target cells. J Immunol 2011; 187(8): 4031-9.
[http://dx.doi.org/10.4049/jimmunol.1101011] [PMID: 21911602]
[59]
Licarete E, Sesarman A, Rauca VF, Luput L, Patras L, Banciu M. HIF-1α acts as a molecular target for simvastatin cytotoxicity in B16.F10 melanoma cells cultured under chemically induced hypoxia. Oncol Lett 2017; 13(5): 3942-50.
[http://dx.doi.org/10.3892/ol.2017.5928] [PMID: 28521491]
[60]
Hajizadeh F, Okoye I, Esmaily M, et al. Hypoxia inducible factors in the tumor microenvironment as therapeutic targets of cancer stem cells. Life Sci 2019; 237: 116952.
[http://dx.doi.org/10.1016/j.lfs.2019.116952] [PMID: 31622608]
[61]
Chen G, Liu B, Yin S, et al. Hypoxia induces an endometrial cancer stem-like cell phenotype via HIF-dependent demethylation of SOX2 mRNA. Oncogenesis 2020; 9(9): 81.
[http://dx.doi.org/10.1038/s41389-020-00265-z] [PMID: 32913192]
[62]
Godet I, Shin YJ, Ju JA, Ye IC, Wang G, Gilkes DM. Fate-mapping post-hypoxic tumor cells reveals a ROS-resistant phenotype that promotes metastasis. Nat Commun 2019; 10(1): 4862.
[http://dx.doi.org/10.1038/s41467-019-12412-1] [PMID: 31649238]
[63]
Liu J, Zhang C, Zhao Y, et al. Parkin targets HIF-1α for ubiquitination and degradation to inhibit breast tumor progression. Nat Commun 2017; 8(1): 1823.
[http://dx.doi.org/10.1038/s41467-017-01947-w] [PMID: 29180628]
[64]
Fares J, Fares MY, Khachfe HH, Salhab HA, Fares Y. Molecular principles of metastasis: a hallmark of cancer revisited. Signal Transduct Target Ther 2020; 5(1): 28.
[http://dx.doi.org/10.1038/s41392-020-0134-x] [PMID: 32296047]
[65]
Xia Y, Jiang L, Zhong T. The role of HIF-1α in chemo-/radioresistant tumors. OncoTargets Ther 2018; 11: 3003-11.
[http://dx.doi.org/10.2147/OTT.S158206] [PMID: 29872312]
[66]
Lequeux A, Noman MZ, Xiao M, et al. Impact of hypoxic tumor microenvironment and tumor cell plasticity on the expression of immune checkpoints. Cancer Lett 2019; 458: 13-20.
[http://dx.doi.org/10.1016/j.canlet.2019.05.021] [PMID: 31136782]
[67]
Daniel SK, Sullivan KM, Labadie KP, Pillarisetty VG. Hypoxia as a barrier to immunotherapy in pancreatic adenocarcinoma. Clin Transl Med 2019; 8(1): 10.
[http://dx.doi.org/10.1186/s40169-019-0226-9] [PMID: 30931508]
[68]
Gonzalez H, Hagerling C, Werb Z. Roles of the immune system in cancer: from tumor initiation to metastatic progression. Genes Dev 2018; 32(19-20): 1267-84.
[http://dx.doi.org/10.1101/gad.314617.118] [PMID: 30275043]
[69]
Mezheyeuski A, Segersten U, Leiss LW, et al. Fibroblasts in urothelial bladder cancer define stroma phenotypes that are associated with clinical outcome. Sci Rep 2020; 10(1): 281.
[http://dx.doi.org/10.1038/s41598-019-55013-0] [PMID: 31937798]
[70]
Baghban R, Roshangar L, Jahanban-Esfahlan R, et al. Tumor microenvironment complexity and therapeutic implications at a glance. Cell Commun Signal 2020; 18(1): 59.
[http://dx.doi.org/10.1186/s12964-020-0530-4] [PMID: 32264958]
[71]
Seidel JA, Otsuka A, Kabashima K. Anti-PD-1 and anti-ctla-4 therapies in cancer: mechanisms of action, efficacy, and limitations. Front Oncol 2018; 8: 86.
[http://dx.doi.org/10.3389/fonc.2018.00086] [PMID: 29644214]
[72]
Sharma P, Allison JP. The future of immune checkpoint therapy. Science 2015; 348(6230): 56-61.
[http://dx.doi.org/10.1126/science.aaa8172] [PMID: 25838373]
[73]
Noman MZ, Desantis G, Janji B, et al. PD-L1 is a novel direct target of HIF-1α, and its blockade under hypoxia enhanced MDSC-mediated T cell activation. J Exp Med 2014; 211(5): 781-90.
[http://dx.doi.org/10.1084/jem.20131916] [PMID: 24778419]
[74]
Barsoum IB, Smallwood CA, Siemens DR, Graham CH. A mechanism of hypoxia-mediated escape from adaptive immunity in cancer cells. Cancer Res 2014; 74(3): 665-74.
[http://dx.doi.org/10.1158/0008-5472.CAN-13-0992] [PMID: 24336068]
[75]
Ray SK, Meshram Y, Mukherjee S. Cancer immunology and car-t cells: a turning point therapeutic approach in colorectal carcinoma with clinical insight. Curr Mol Med 2021; 21(3): 221-36.
[http://dx.doi.org/10.2174/1566524020666200824103749] [PMID: 32838717]
[76]
Alsaab HO, Sau S, Alzhrani R, et al. PD-1 and PD-L1 Checkpoint signaling inhibition for cancer immunotherapy: mechanism, combinations, and clinical outcome. Front Pharmacol 2017; 8: 561.
[http://dx.doi.org/10.3389/fphar.2017.00561] [PMID: 28878676]
[77]
Akinleye A, Rasool Z. Immune checkpoint inhibitors of PD-L1 as cancer therapeutics. J Hematol Oncol 2019; 12(1): 92.
[http://dx.doi.org/10.1186/s13045-019-0779-5] [PMID: 31488176]
[78]
Pietrobon V, Marincola FM. Hypoxia and the phenomenon of immune exclusion. J Transl Med 2021; 19(1): 9.
[http://dx.doi.org/10.1186/s12967-020-02667-4] [PMID: 33407613]
[79]
Black M, Barsoum IB, Truesdell P, et al. Activation of the PD-1/PD-L1 immune checkpoint confers tumor cell chemoresistance associated with increased metastasis. Oncotarget 2016; 7(9): 10557-67.
[http://dx.doi.org/10.18632/oncotarget.7235] [PMID: 26859684]
[80]
Groth C, Hu X, Weber R, et al. Immunosuppression mediated by myeloid-derived suppressor cells (MDSCs) during tumour progression. Br J Cancer 2019; 120(1): 16-25.
[http://dx.doi.org/10.1038/s41416-018-0333-1] [PMID: 30413826]
[81]
Palsson-McDermott EM, Dyck L, Zasłona Z, et al. Pyruvate kinase M2 is required for the expression of the immune checkpoint PD-L1 in immune cells and tumors. Front Immunol 2017; 8: 1300.
[http://dx.doi.org/10.3389/fimmu.2017.01300] [PMID: 29081778]
[82]
Pinato DJ, Black JR, Trousil S, et al. Programmed cell death ligands expression in phaeochromocytomas and paragangliomas: Relationship with the hypoxic response, immune evasion and malignant behavior. OncoImmunology 2017; 6(11): e1358332.
[http://dx.doi.org/10.1080/2162402X.2017.1358332] [PMID: 29147618]
[83]
Jaiswal S, Jamieson CH, Pang WW, et al. CD47 is upregulated on circulating hematopoietic stem cells and leukemia cells to avoid phagocytosis. Cell 2009; 138(2): 271-85.
[http://dx.doi.org/10.1016/j.cell.2009.05.046] [PMID: 19632178]
[84]
Zhao H, Wang J, Kong X, et al. CD47 promotes tumor invasion and metastasis in non-small cell lung cancer. Sci Rep 2016; 6: 29719.
[http://dx.doi.org/10.1038/srep29719] [PMID: 27411490]
[85]
Zhou Y, Yao Y, Deng Y, Shao A. Regulation of efferocytosis as a novel cancer therapy. Cell Commun Signal 2020; 18(1): 71.
[http://dx.doi.org/10.1186/s12964-020-00542-9] [PMID: 32370748]
[86]
Sprooten J, De Wijngaert P, Vanmeerbeerk I, et al. Necroptosis in immuno-oncology and cancer immunotherapy. Cells 2020; 9(8): 1823.
[http://dx.doi.org/10.3390/cells9081823] [PMID: 32752206]
[87]
Zhang H, Lu H, Xiang L, et al. HIF-1 regulates CD47 expression in breast cancer cells to promote evasion of phagocytosis and maintenance of cancer stem cells. Proc Natl Acad Sci USA 2015; 112(45): E6215-23.
[http://dx.doi.org/10.1073/pnas.1520032112] [PMID: 26512116]
[88]
Ray SK, Mukherjee S. Mitophagy in carcinogenesis and tumor progression- a new paradigm with emerging importance. Anticancer Agents Med Chem 2021; 21(16): 2130-41.
[http://dx.doi.org/10.2174/1871520621666210112121910] [PMID: 33438558]
[89]
Daskalaki I, Gkikas I, Tavernarakis N. Hypoxia and selective autophagy in cancer development and therapy. Front Cell Dev Biol 2018; 6: 104.
[http://dx.doi.org/10.3389/fcell.2018.00104] [PMID: 30250843]
[90]
Vega-Rubín-de-Celis S. The role of beclin 1-dependent autophagy in cancer. Biology (Basel) 2019; 9(1): 4.
[http://dx.doi.org/10.3390/biology9010004] [PMID: 31877888]
[91]
Janji B, Berchem G, Chouaib S. Targeting autophagy in the tumor microenvironment: new challenges and opportunities for regulating tumor immunity. Front Immunol 2018; 9: 887.
[http://dx.doi.org/10.3389/fimmu.2018.00887] [PMID: 29922284]
[92]
Yang L, Shi P, Zhao G, et al. Targeting cancer stem cell pathways for cancer therapy. Signal Transduct Target Ther 2020; 5(1): 8.
[http://dx.doi.org/10.1038/s41392-020-0110-5] [PMID: 32296030]
[93]
Antebi B, Rodriguez LA II, Walker KP III, et al. Short-term physiological hypoxia potentiates the therapeutic function of mesenchymal stem cells. Stem Cell Res Ther 2018; 9(1): 265.
[http://dx.doi.org/10.1186/s13287-018-1007-x] [PMID: 30305185]
[94]
Hasmim M, Janji B, Khaled M, et al. Cutting Edge: NANOG activates autophagy under hypoxic stress by binding to bnip3l promoter. J Immunol 2017; 198(4): 1423-8.
[http://dx.doi.org/10.4049/jimmunol.1600981] [PMID: 28093523]
[95]
Wang B, Zhao Q, Zhang Y, et al. Targeting hypoxia in the tumor microenvironment: a potential strategy to improve cancer immunotherapy. J Exp Clin Cancer Res 2021; 40(1): 24.
[http://dx.doi.org/10.1186/s13046-020-01820-7] [PMID: 33422072]
[96]
Ou ZL, Luo Z, Wei W, Liang S, Gao TL, Lu YB. Hypoxia-induced shedding of MICA and HIF1A-mediated immune escape of pancreatic cancer cells from NK cells: role of circ_0000977/miR-153 axis. RNA Biol 2019; 16(11): 1592-603.
[http://dx.doi.org/10.1080/15476286.2019.1649585] [PMID: 31402756]
[97]
Sordo-Bahamonde C, Lorenzo-Herrero S, Payer ÁR, Gonzalez S, López-Soto A. Mechanisms of apoptosis resistance to nk cell-mediated cytotoxicity in cancer. Int J Mol Sci 2020; 21(10): 3726.
[http://dx.doi.org/10.3390/ijms21103726] [PMID: 32466293]
[98]
Andersson E, Poschke I, Villabona L, et al. Non-classical HLA-class I expression in serous ovarian carcinoma: Correlation with the HLA-genotype, tumor infiltrating immune cells and prognosis. OncoImmunology 2015; 5(1): e1052213.
[http://dx.doi.org/10.1080/2162402X.2015.1052213] [PMID: 26942060]
[99]
Kren L, Slaby O, Muckova K, et al. Expression of immune-modulatory molecules HLA-G and HLA-E by tumor cells in glioblastomas: an unexpected prognostic significance? Neuropathology 2011; 31(2): 129-34.
[http://dx.doi.org/10.1111/j.1440-1789.2010.01149.x] [PMID: 20667016]
[100]
Carosella ED, Favier B, Rouas-Freiss N, Moreau P, Lemaoult J. Beyond the increasing complexity of the immunomodulatory HLA-G molecule. Blood 2008; 111(10): 4862-70.
[http://dx.doi.org/10.1182/blood-2007-12-127662] [PMID: 18334671]
[101]
Amodio G, Sales de Albuquerque R, Gregori S. New insights into HLA-G mediated tolerance. Tissue Antigens 2014; 84(3): 255-63.
[http://dx.doi.org/10.1111/tan.12427] [PMID: 25132109]
[102]
Garziera M, Scarabel L, Toffoli G. Hypoxic modulation of HLA-G expression through the metabolic sensor HIF-1 in human cancer cells. J Immunol Res 2017; 2017: 4587520.
[http://dx.doi.org/10.1155/2017/4587520] [PMID: 28781970]
[103]
Guo ZY, Lv YG, Wang L, et al. Predictive value of HLA-G and HLA-E in the prognosis of colorectal cancer patients. Cell Immunol 2015; 293(1): 10-6.
[http://dx.doi.org/10.1016/j.cellimm.2014.10.003] [PMID: 25461612]
[104]
Yaghi L, Poras I, Simoes RT, et al. Hypoxia inducible factor-1 mediates the expression of the immune checkpoint HLA-G in glioma cells through hypoxia response element located in exon 2. Oncotarget 2016; 7(39): 63690-707.
[http://dx.doi.org/10.18632/oncotarget.11628] [PMID: 27577073]
[105]
Ferns DM, Heeren AM, Samuels S, et al. Classical and non-classical HLA class I aberrations in primary cervical squamous- and adenocarcinomas and paired lymph node metastases. J Immunother Cancer 2016; 4: 78.
[http://dx.doi.org/10.1186/s40425-016-0184-3] [PMID: 27895918]
[106]
Sasaki T, Kanaseki T, Shionoya Y, et al. Microenvironmental stresses induce HLA-E/Qa-1 surface expression and thereby reduce CD8(+) T-cell recognition of stressed cells. Eur J Immunol 2016; 46(4): 929-40.
[http://dx.doi.org/10.1002/eji.201545835] [PMID: 26711740]
[107]
Xie H, Simon MC. Oxygen availability and metabolic reprogramming in cancer. J Biol Chem 2017; 292(41): 16825-32.
[http://dx.doi.org/10.1074/jbc.R117.799973] [PMID: 28842498]
[108]
Samec M, Liskova A, Koklesova L, et al. Flavonoids targeting hif-1: implications on cancer metabolism. Cancers (Basel) 2021; 13(1): E130.
[http://dx.doi.org/10.3390/cancers13010130] [PMID: 33401572]
[109]
Huber V, Camisaschi C, Berzi A, et al. Cancer acidity: An ultimate frontier of tumor immune escape and a novel target of immunomodulation. Semin Cancer Biol 2017; 43: 74-89.
[http://dx.doi.org/10.1016/j.semcancer.2017.03.001] [PMID: 28267587]
[110]
McDonald PC, Dedhar S. Carbonic anhydrase IX (CAIX) as a mediator of hypoxia-induced stress response in cancer cells. Subcell Biochem 2014; 75: 255-69.
[http://dx.doi.org/10.1007/978-94-007-7359-2_13] [PMID: 24146383]
[111]
Pastorek J, Pastorekova S. Hypoxia-induced carbonic anhydrase IX as a target for cancer therapy: from biology to clinical use. Semin Cancer Biol 2015; 31: 52-64.
[http://dx.doi.org/10.1016/j.semcancer.2014.08.002] [PMID: 25117006]
[112]
Nakagawa Y, Negishi Y, Shimizu M, Takahashi M, Ichikawa M, Takahashi H. Effects of extracellular pH and hypoxia on the function and development of antigen-specific cytotoxic T lymphocytes. Immunol Lett 2015; 167(2): 72-86.
[http://dx.doi.org/10.1016/j.imlet.2015.07.003] [PMID: 26209187]
[113]
Aghi MK, Liu TC, Rabkin S, Martuza RL. Hypoxia enhances the replication of oncolytic herpes simplex virus. Mol Ther 2009; 17(1): 51-6.
[http://dx.doi.org/10.1038/mt.2008.232] [PMID: 18957963]
[114]
Wigerup C, Påhlman S, Bexell D. Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer. Pharmacol Ther 2016; 164: 152-69.
[http://dx.doi.org/10.1016/j.pharmthera.2016.04.009] [PMID: 27139518]
[115]
Yu T, Tang B, Sun X. Development of inhibitors targeting hypoxia-inducible factor 1 and 2 for cancer therapy. Yonsei Med J 2017; 58(3): 489-96.
[http://dx.doi.org/10.3349/ymj.2017.58.3.489] [PMID: 28332352]
[116]
Fallah J, Rini BI. HIF inhibitors: status of current clinical development. Curr Oncol Rep 2019; 21(1): 6.
[http://dx.doi.org/10.1007/s11912-019-0752-z] [PMID: 30671662]
[117]
Ban HS, Kim BK, Lee H, et al. The novel hypoxia-inducible factor-1α inhibitor IDF-11774 regulates cancer metabolism, thereby suppressing tumor growth. Cell Death Dis 2017; 8(6): e2843.
[http://dx.doi.org/10.1038/cddis.2017.235] [PMID: 28569777]
[118]
Mistry IN, Thomas M, Calder EDD, Conway SJ, Hammond EM. Clinical advances of hypoxia-activated prodrugs in combination with radiation therapy. Int J Radiat Oncol Biol Phys 2017; 98(5): 1183-96.
[http://dx.doi.org/10.1016/j.ijrobp.2017.03.024] [PMID: 28721903]
[119]
Murciano-Goroff YR, Warner AB, Wolchok JD. The future of cancer immunotherapy: microenvironment-targeting combinations. Cell Res 2020; 30(6): 507-19.
[http://dx.doi.org/10.1038/s41422-020-0337-2] [PMID: 32467593]
[120]
Sodergren MH, Mangal N, Wasan H, et al. Immunological combination treatment holds the key to improving survival in pancreatic cancer. J Cancer Res Clin Oncol 2020; 146(11): 2897-911.
[http://dx.doi.org/10.1007/s00432-020-03332-5] [PMID: 32748119]
[121]
Baran N, Konopleva M. Molecular pathways: hypoxia-activated prodrugs in cancer therapy. Clin Cancer Res 2017; 23(10): 2382-90.
[http://dx.doi.org/10.1158/1078-0432.CCR-16-0895] [PMID: 28137923]
[122]
Xu F, Na L, Li Y, Chen L. Roles of the PI3K/AKT/mTOR signalling pathways in neurodegenerative diseases and tumours. Cell Biosci 2020; 10(1): 54.
[http://dx.doi.org/10.1186/s13578-020-00416-0] [PMID: 32266056]
[123]
Brugarolas JB, Vazquez F, Reddy A, Sellers WR, Kaelin WG Jr. TSC2 regulates VEGF through mTOR-dependent and -independent pathways. Cancer Cell 2003; 4(2): 147-58.
[http://dx.doi.org/10.1016/S1535-6108(03)00187-9] [PMID: 12957289]
[124]
Lastwika KJ, Wilson W III, Li QK, et al. Control of PD-L1 expression by oncogenic activation of the AKT-mTOR pathway in non-small cell lung cancer. Cancer Res 2016; 76(2): 227-38.
[http://dx.doi.org/10.1158/0008-5472.CAN-14-3362] [PMID: 26637667]
[125]
Song M, Chen D, Lu B, et al. PTEN loss increases PD-L1 protein expression and affects the correlation between PD-L1 expression and clinical parameters in colorectal cancer. PLoS One 2013; 8(6): e65821.
[http://dx.doi.org/10.1371/journal.pone.0065821] [PMID: 23785454]
[126]
Zhao L, Li C, Liu F, et al. A blockade of PD-L1 produced antitumor and antimetastatic effects in an orthotopic mouse pancreatic cancer model via the PI3K/Akt/mTOR signaling pathway. OncoTargets Ther 2017; 10: 2115-26.
[http://dx.doi.org/10.2147/OTT.S130481] [PMID: 28442920]
[127]
Terry S, Faouzi Zaarour R, Hassan Venkatesh G, et al. Role of hypoxic stress in regulating tumor immunogenicity, resistance and plasticity. Int J Mol Sci 2018; 19(10): 3044.
[http://dx.doi.org/10.3390/ijms19103044] [PMID: 30301213]
[128]
Hunter FW, Wouters BG, Wilson WR. Hypoxia-activated prodrugs: paths forward in the era of personalised medicine. Br J Cancer 2016; 114(10): 1071-7.
[http://dx.doi.org/10.1038/bjc.2016.79] [PMID: 27070712]
[129]
Hendricksen K, Cornel EB, de Reijke TM, Arentsen HC, Chawla S, Witjes JA. Phase 2 study of adjuvant intravesical instillations of apaziquone for high risk nonmuscle invasive bladder cancer. J Urol 2012; 187(4): 1195-9.
[http://dx.doi.org/10.1016/j.juro.2011.11.101] [PMID: 22335860]
[130]
Bhattarai D, Xu X, Lee K. Hypoxia-inducible factor-1 (HIF-1) inhibitors from the last decade (2007 to 2016): A “structure-activity relationship” perspective. Med Res Rev 2018; 38(4): 1404-42.
[http://dx.doi.org/10.1002/med.21477] [PMID: 29278273]
[131]
Powis G, Kirkpatrick L. Hypoxia inducible factor-1alpha as a cancer drug target. Mol Cancer Ther 2004; 3(5): 647-54.
[PMID: 15141023]
[132]
Mabjeesh NJ, Escuin D, LaVallee TM, et al. 2ME2 inhibits tumor growth and angiogenesis by disrupting microtubules and dysregulating HIF. Cancer Cell 2003; 3(4): 363-75.
[http://dx.doi.org/10.1016/S1535-6108(03)00077-1] [PMID: 12726862]
[133]
Rapisarda A, Uranchimeg B, Scudiero DA, et al. Identification of small molecule inhibitors of hypoxia-inducible factor 1 transcriptional activation pathway. Cancer Res 2002; 62(15): 4316-24.
[PMID: 12154035]
[134]
Kooshkaki O, Derakhshani A, Hosseinkhani N, et al. Combination of ipilimumab and nivolumab in cancers: from clinical practice to ongoing clinical trials. Int J Mol Sci 2020; 21(12): 4427.
[http://dx.doi.org/10.3390/ijms21124427] [PMID: 32580338]
[135]
Lee HT, Lee SH, Heo YS. Molecular interactions of antibody drugs targeting pd-1, pd-l1, and ctla-4 in immuno-oncology. Molecules 2019; 24(6): 1190.
[http://dx.doi.org/10.3390/molecules24061190] [PMID: 30917623]
[136]
Hellmann MD, Paz-Ares L, Bernabe Caro R, et al. Nivolumab plus Ipilimumab in advanced non-small-cell lung cancer. N Engl J Med 2019; 381(21): 2020-31.
[http://dx.doi.org/10.1056/NEJMoa1910231] [PMID: 31562796]
[137]
Ray SK, Mukherjee S. Current headway in cancer immunotherapy emphasising the practice of genetically engineered t-cells to target selected tumor antigen. Critical Rev Immunol 2020; 23-40.
[http://dx.doi.org/10.1615/CritRevImmunol.2020037044]
[138]
Noman MZ, Janji B, Berchem G, Mami-Chouaib F, Chouaib S. Hypoxia-induced autophagy: a new player in cancer immunotherapy? Autophagy 2012; 8(4): 704-6.
[http://dx.doi.org/10.4161/auto.19572] [PMID: 22441015]
[139]
Chan MC, Holt-Martyn JP, Schofield CJ, Ratcliffe PJ. Pharmacological targeting of the HIF hydroxylases-A new field in medicine development. Mol Aspects Med 2016; 47-48: 54-75.
[http://dx.doi.org/10.1016/j.mam.2016.01.001] [PMID: 26791432]
[140]
Haase VH. Therapeutic targeting of the HIF oxygen-sensing pathway: Lessons learned from clinical studies. Exp Cell Res 2017; 356(2): 160-5.
[http://dx.doi.org/10.1016/j.yexcr.2017.05.004] [PMID: 28483447]
[141]
Noman MZ, Hasmim M, Lequeux A, et al. Improving cancer immunotherapy by targeting the hypoxic tumor microenvironment: new opportunities and challenges. Cells 2019; 8(9): 1083.
[http://dx.doi.org/10.3390/cells8091083] [PMID: 31540045]
[142]
Shorning BY, Dass MS, Smalley MJ, Pearson HB. The PI3K-AKT-mTOR pathway and prostate cancer: at the crossroads of AR, MAPK, and WNT signaling. Int J Mol Sci 2020; 21(12): 4507.
[http://dx.doi.org/10.3390/ijms21124507] [PMID: 32630372]
[143]
Bohonowych JE, Peng S, Gopal U, et al. Comparative analysis of novel and conventional Hsp90 inhibitors on HIF activity and angiogenic potential in clear cell renal cell carcinoma: implications for clinical evaluation. BMC Cancer 2011; 11: 520.
[http://dx.doi.org/10.1186/1471-2407-11-520] [PMID: 22172030]

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