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Review Article

Mechanisms of PD-L1 Regulation in Tumor Immune Ecosystem

Journal of Biomedical Research & Environmental Sciences article abstract with citation details, DOI, publication dates, subject areas, full text links, and references.

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Article Type Review Article
Subject Biology Group
OCLC JBRES Record
Fatima Bangash*, Sabiha Alia and Rabia Gul
Issue: Volume3-Issue8
Pages: 867-879
Received: 2022-07-15
Accepted: 2022-07-30
Published: 2022-08-09

Abstract

PD-1 (Programmed Death Receptor-1) is a cell membrane protein found on Cytotoxic T cells (CTLs) surface. An abundantly expressed type I transmembrane protein in healthy tissues, Programmed Death-Ligand 1 (PD-L1), has a molecular mass of 40 kDa. The extracellular binding of the proteins PD-1 and PD-L1 prevents the development of autoimmune disorders by suppressing the activation of CTLs under normal physiological conditions. It has been shown that cancer cells can avoid immune monitoring by increasing PD-1/PD-1-mediated CTL inactivation in melanoma, lung cancer, renal cell carcinoma, and other malignant tumors. PD-L1 expression regulation has been described in recent years from the standpoint of gene amplification, chromatin modification, post-transcription and transcription modification, translation, and post-translational modification. Anti-PD-1 immunotherapy has demonstrated promising results in treating several cancers, including breast, lung, and prostate cancers. This review aims to present the most recent research findings in PD-L1 regulation in cancer cells. A tumor immunotherapy strategy targeting PD-1 and PD-L1 is expected to be useful.

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© 2022 Bangash F, et al. Distributed under Creative Commons CC-BY 4.0 Creative CommonsAttribution

How to cite this article

Bangash F, Alia S, Gul R. Mechanisms of PD-L1 Regulation in Tumor Immune Ecosystem. J Biomed Res Environ Sci. 2022 Aug 09; 3(8): 867-879. doi: 10.37871/jbres1525, Article ID: JBRES1525, Available at: https://www.jelsciences.com/articles/jbres1525.pdf

Subject area(s)

Molecular BiologyGenetics

References

  1. Escors D, Gato-Cañas M, Zuazo M, Arasanz H, García-Granda MJ, Vera R, Kochan G. The intracellular signalosome of PD-L1 in cancer cells. Signal Transduct Target Ther. 2018 Sep 28;3:26. doi: 10.1038/s41392-018-0022-9. PMID: 30275987; PMCID: PMC6160488.
  2. Dong H, Zhu G, Tamada K, Chen L. B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat Med. 1999 Dec;5(12):1365-9. doi: 10.1038/70932. PMID: 10581077.
  3. Woods DM, Sodré AL, Villagra A, Sarnaik A, Sotomayor EM, Weber J. HDAC Inhibition Upregulates PD-1 Ligands in Melanoma and Augments Immunotherapy with PD-1 Blockade. Cancer Immunol Res. 2015 Dec;3(12):1375-85. doi: 10.1158/2326-6066.CIR-15-0077-T. Epub 2015 Aug 21. PMID: 26297712; PMCID: PMC4674300.
  4. M L, P PV, T K, M P, E S, J P, K V W, C L, F C, S D, M SKS, M M, A K, J PI, A S, E S, J W, E M S, A V. Essential role of HDAC6 in the regulation of PD-L1 in melanoma. Mol Oncol. 2016 May;10(5):735-750. doi: 10.1016/j.molonc.2015.12.012. Epub 2016 Jan 6. PMID: 26775640; PMCID: PMC4870131.
  5. Khan Safir Ullah. Extra Chromosomal Circular DNA: Recent Advances in Research. Journal of Biomedical Research & Environmental Sciences. 2022.
  6. Zhu H, Bengsch F, Svoronos N, Rutkowski MR, Bitler BG, Allegrezza MJ, Yokoyama Y, Kossenkov AV, Bradner JE, Conejo-Garcia JR, Zhang R. BET Bromodomain Inhibition Promotes Anti-tumor Immunity by Suppressing PD-L1 Expression. Cell Rep. 2016 Sep 13;16(11):2829-2837. doi: 10.1016/j.celrep.2016.08.032. PMID: 27626654; PMCID: PMC5177024.
  7. Zak KM, Grudnik P, Magiera K, Dömling A, Dubin G, Holak TA. Structural Biology of the Immune Checkpoint Receptor PD-1 and Its Ligands PD-L1/PD-L2. Structure. 2017 Aug 1;25(8):1163-1174. doi: 10.1016/j.str.2017.06.011. PMID: 28768162.
  8. Pascolutti R, Sun X, Kao J, Maute RL, Ring AM, Bowman GR, Kruse AC. Structure and Dynamics of PD-L1 and an Ultra-High-Affinity PD-1 Receptor Mutant. Structure. 2016 Oct 4;24(10):1719-1728. doi: 10.1016/j.str.2016.06.026. Epub 2016 Sep 8. PMID: 27618663; PMCID: PMC5052120.
  9. Lázár-Molnár E, Scandiuzzi L, Basu I, Quinn T, Sylvestre E, Palmieri E, Ramagopal UA, Nathenson SG, Guha C, Almo SC. Structure-guided development of a high-affinity human Programmed Cell Death-1: Implications for tumor immunotherapy. EBioMedicine. 2017 Mar;17:30-44. doi: 10.1016/j.ebiom.2017.02.004. Epub 2017 Feb 6. PMID: 28233730; PMCID: PMC5360572.
  10. Wang Y, Wang H, Yao H, Li C, Fang JY, Xu J. Regulation of PD-L1: Emerging Routes for Targeting Tumor Immune Evasion. Front Pharmacol. 2018 May 22;9:536. doi: 10.3389/fphar.2018.00536. PMID: 29910728; PMCID: PMC5992436.
  11. Wang W, Li F, Mao Y, Zhou H, Sun J, Li R, Liu C, Chen W, Hua D, Zhang X. A miR-570 binding site polymorphism in the B7-H1 gene is associated with the risk of gastric adenocarcinoma. Hum Genet. 2013 Jun;132(6):641-8. doi: 10.1007/s00439-013-1275-6. Epub 2013 Feb 21. PMID: 23430453.
  12. Shin DS, Zaretsky JM, Escuin-Ordinas H, Garcia-Diaz A, Hu-Lieskovan S, Kalbasi A, Grasso CS, Hugo W, Sandoval S, Torrejon DY, Palaskas N, Rodriguez GA, Parisi G, Azhdam A, Chmielowski B, Cherry G, Seja E, Berent-Maoz B, Shintaku IP, Le DT, Pardoll DM, Diaz LA Jr, Tumeh PC, Graeber TG, Lo RS, Comin-Anduix B, Ribas A. Primary Resistance to PD-1 Blockade Mediated by JAK1/2 Mutations. Cancer Discov. 2017 Feb;7(2):188-201. doi: 10.1158/2159-8290.CD-16-1223. Epub 2016 Nov 30. PMID: 27903500; PMCID: PMC5296316.
  13. George J, Saito M, Tsuta K, Iwakawa R, Shiraishi K, Scheel AH, Uchida S, Watanabe SI, Nishikawa R, Noguchi M, Peifer M, Jang SJ, Petersen I, Büttner R, Harris CC, Yokota J, Thomas RK, Kohno T. Genomic Amplification of CD274 (PD-L1) in Small-Cell Lung Cancer. Clin Cancer Res. 2017 Mar 1;23(5):1220-1226. doi: 10.1158/1078-0432.CCR-16-1069. Epub 2016 Sep 12. PMID: 27620277; PMCID: PMC6329376.
  14. Clavé S, Pijuan L, Casadevall D, Taus Á, Gimeno J, Hernández-Llodrà S, Rodríguez-Rivera M, Lorenzo M, Menéndez S, Albanell J, Espinet B, Arriola E, Salido M. CD274 (PDL1) and JAK2 genomic amplifications in pulmonary squamous-cell and adenocarcinoma patients. Histopathology. 2018 Jan;72(2):259-269. doi: 10.1111/his.13339. Epub 2017 Oct 27. PMID: 28795418.
  15. Ikeda S, Okamoto T, Okano S, Umemoto Y, Tagawa T, Morodomi Y, Kohno M, Shimamatsu S, Kitahara H, Suzuki Y, Fujishita T, Maehara Y. PD-L1 Is Upregulated by Simultaneous Amplification of the PD-L1 and JAK2 Genes in Non-Small Cell Lung Cancer. J Thorac Oncol. 2016 Jan;11(1):62-71. doi: 10.1016/j.jtho.2015.09.010. PMID: 26762740.
  16. Kress TR, Sabò A, Amati B. MYC: connecting selective transcriptional control to global RNA production. Nat Rev Cancer. 2015 Oct;15(10):593-607. doi: 10.1038/nrc3984. Epub 2015 Sep 18. PMID: 26383138.
  17. Shi Y. Regulatory mechanisms of PD-L1 expression in cancer cells. Cancer Immunol Immunother. 2018 Oct;67(10):1481-1489. doi: 10.1007/s00262-018-2226-9. Epub 2018 Aug 17. PMID: 30120503.
  18. Khan SU, Khan MU. The mechanism of mammalian mitochondrial quality control system. Journal of Chemistry and Nutritional Biochemistry. 2021;59-69. doi: 10.48185/jcnb.v2i2.387.
  19. KATAOKA K, SHIRAISHI Y, TAKEDA Y, Aberrant PD-L1 expression through 3′-UTR disruption in multiple cancers. Nature. 2016:534(7607):402-406.
  20. Green MR, Rodig S, Juszczynski P, Ouyang J, Sinha P, O'Donnell E, Neuberg D, Shipp MA. Constitutive AP-1 activity and EBV infection induce PD-L1 in Hodgkin lymphomas and posttransplant lymphoproliferative disorders: implications for targeted therapy. Clin Cancer Res. 2012 Mar 15;18(6):1611-8. doi: 10.1158/1078-0432.CCR-11-1942. Epub 2012 Jan 23. Erratum in: Clin Cancer Res. 2012 Apr 1;18(7):2117. PMID: 22271878; PMCID: PMC3321508.
  21. Fang W, Zhang J, Hong S, Zhan J, Chen N, Qin T, Tang Y, Zhang Y, Kang S, Zhou T, Wu X, Liang W, Hu Z, Ma Y, Zhao Y, Tian Y, Yang Y, Xue C, Yan Y, Hou X, Huang P, Huang Y, Zhao H, Zhang L. EBV-driven LMP1 and IFN-γ up-regulate PD-L1 in nasopharyngeal carcinoma: Implications for oncotargeted therapy. Oncotarget. 2014 Dec 15;5(23):12189-202. doi: 10.18632/oncotarget.2608. PMID: 25361008; PMCID: PMC4322961.
  22. Garcia-Diaz A, Shin DS, Moreno BH, Saco J, Escuin-Ordinas H, Rodriguez GA, Zaretsky JM, Sun L, Hugo W, Wang X, Parisi G, Saus CP, Torrejon DY, Graeber TG, Comin-Anduix B, Hu-Lieskovan S, Damoiseaux R, Lo RS, Ribas A. Interferon Receptor Signaling Pathways Regulating PD-L1 and PD-L2 Expression. Cell Rep. 2017 May 9;19(6):1189-1201. doi: 10.1016/j.celrep.2017.04.031. Erratum in: Cell Rep. 2019 Dec 10;29(11):3766. PMID: 28494868; PMCID: PMC6420824.
  23. Khan SU, Khan MU, Kalsoom F, Khan MI, Gao S, Unar A, Zubair M, Bilal M. Mechanisms of gene regulation by histone degradation in adaptation of yeast: an overview of recent advances. Arch Microbiol. 2022 Apr 28;204(5):287. doi: 10.1007/s00203-022-02897-8. PMID: 35482104.
  24. Lim SO, Li CW, Xia W, Cha JH, Chan LC, Wu Y, Chang SS, Lin WC, Hsu JM, Hsu YH, Kim T, Chang WC, Hsu JL, Yamaguchi H, Ding Q, Wang Y, Yang Y, Chen CH, Sahin AA, Yu D, Hortobagyi GN, Hung MC. Deubiquitination and Stabilization of PD-L1 by CSN5. Cancer Cell. 2016 Dec 12;30(6):925-939. doi: 10.1016/j.ccell.2016.10.010. Epub 2016 Nov 17. PMID: 27866850; PMCID: PMC5171205.
  25. Wang X, Yang L, Huang F, Zhang Q, Liu S, Ma L, You Z. Inflammatory cytokines IL-17 and TNF-α up-regulate PD-L1 expression in human prostate and colon cancer cells. Immunol Lett. 2017 Apr;184:7-14. doi: 10.1016/j.imlet.2017.02.006. Epub 2017 Feb 14. PMID: 28223102; PMCID: PMC5362328.
  26. Marzec M, Zhang Q, Goradia A, Raghunath PN, Liu X, Paessler M, Wang HY, Wysocka M, Cheng M, Ruggeri BA, Wasik MA. Oncogenic kinase NPM/ALK induces through STAT3 expression of immunosuppressive protein CD274 (PD-L1, B7-H1). Proc Natl Acad Sci U S A. 2008 Dec 30;105(52):20852-7. doi: 10.1073/pnas.0810958105. Epub 2008 Dec 16. PMID: 19088198; PMCID: PMC2634900.
  27. Lee SJ, Jang BC, Lee SW, Yang YI, Suh SI, Park YM, Oh S, Shin JG, Yao S, Chen L, Choi IH. Interferon regulatory factor-1 is prerequisite to the constitutive expression and IFN-gamma-induced upregulation of B7-H1 (CD274). FEBS Lett. 2006 Feb 6;580(3):755-62. doi: 10.1016/j.febslet.2005.12.093. Epub 2006 Jan 9. PMID: 16413538.
  28. Li N, Wang J, Zhang N, Zhuang M, Zong Z, Zou J, Li G, Wang X, Zhou H, Zhang L, Shi Y. Cross-talk between TNF-α and IFN-γ signaling in induction of B7-H1 expression in hepatocellular carcinoma cells. Cancer Immunol Immunother. 2018 Feb;67(2):271-283. doi: 10.1007/s00262-017-2086-8. Epub 2017 Oct 31. PMID: 29090321.
  29. Concha-Benavente F, Srivastava R M, Trivedi S. Identification of the cell-intrinsic and -extrinsic pathways downstream of EGFR and IFNgamma that induce PD-L1 expres-sion in head and neck cancer. Cancer Res. 2016:76(5):1031-43.
  30. Khan S, Khan M. Molecular developments in cell models of fatty liver disease. DYSONALife Science. 2022;1:16-29. doi: 10.30493/DLS.2022.325915.
  31. Moon JW, Kong SK, Kim BS, Kim HJ, Lim H, Noh K, Kim Y, Choi JW, Lee JH, Kim YS. IFNγ induces PD-L1 overexpression by JAK2/STAT1/IRF-1 signaling in EBV-positive gastric carcinoma. Sci Rep. 2017 Dec 19;7(1):17810. doi: 10.1038/s41598-017-18132-0. PMID: 29259270; PMCID: PMC5736657.
  32. Liu J, Hamrouni A, Wolowiec D, Coiteux V, Kuliczkowski K, Hetuin D, Saudemont A, Quesnel B. Plasma cells from multiple myeloma patients express B7-H1 (PD-L1) and increase expression after stimulation with IFN-{gamma} and TLR ligands via a MyD88-, TRAF6-, and MEK-dependent pathway. Blood. 2007 Jul 1;110(1):296-304. doi: 10.1182/blood-2006-10-051482. Epub 2007 Mar 15. PMID: 17363736.
  33. Okita R, Maeda A, Shimizu K, Nojima Y, Saisho S, Nakata M. PD-L1 overexpression is partially regulated by EGFR/HER2 signaling and associated with poor prognosis in patients with non-small-cell lung cancer. Cancer Immunol Immunother. 2017 Jul;66(7):865-876. doi: 10.1007/s00262-017-1986-y. Epub 2017 Mar 25. PMID: 28341875.
  34. Khan SU. Therapeutic application of genetically engineered ribosome-inactivating toxin proteins for cancer. J Biomed Res Environ Sci. 2021;2(12):1216-1228. doi:10.37871/jbres1375.
  35. Fiedler M, Schulz D, Piendl G, Brockhoff G, Eichberger J, Menevse AN, Beckhove P, Hautmann M, Reichert TE, Ettl T, Bauer RJ. Buparlisib modulates PD-L1 expression in head and neck squamous cell carcinoma cell lines. Exp Cell Res. 2020 Nov 1;396(1):112259. doi: 10.1016/j.yexcr.2020.112259. Epub 2020 Sep 6. PMID: 32898555.
  36. Sumimoto H, Takano A, Teramoto K, Daigo Y. RAS-Mitogen-Activated Protein Kinase Signal Is Required for Enhanced PD-L1 Expression in Human Lung Cancers. PLoS One. 2016 Nov 15;11(11):e0166626. doi: 10.1371/journal.pone.0166626. PMID: 27846317; PMCID: PMC5112979.
  37. Khan SU, Khan MU. Review on gene regulation: DNA-protein and protein-protein interactions and their regulatory elements. Journal of Chemistry and Nutritional Biochemistry. 2021;2(2):35-45. doi: 10.48185/jcnb.v2i2.378.
  38. Wu Y, Zhang C, Liu X, He Z, Shan B, Zeng Q, Zhao Q, Zhu H, Liao H, Cen X, Xu X, Zhang M, Hou T, Wang Z, Yan H, Yang S, Sun Y, Chen Y, Wu R, Xie T, Chen W, Najafov A, Ying S, Xia H. ARIH1 signaling promotes anti-tumor immunity by targeting PD-L1 for proteasomal degradation. Nat Commun. 2021 Apr 20;12(1):2346. doi: 10.1038/s41467-021-22467-8. PMID: 33879767; PMCID: PMC8058344.
  39. Yang L, Huang F, Mei J, Wang X, Zhang Q, Wang H, Xi M, You Z. Posttranscriptional Control of PD-L1 Expression by 17β-Estradiol via PI3K/Akt Signaling Pathway in ERα-Positive Cancer Cell Lines. Int J Gynecol Cancer. 2017 Feb;27(2):196-205. doi: 10.1097/IGC.0000000000000875. PMID: 27870715; PMCID: PMC5258765.
  40. Quandt D, Jasinski-Bergner S, Müller U, Schulze B, Seliger B. Synergistic effects of IL-4 and TNFα on the induction of B7-H1 in renal cell carcinoma cells inhibiting allogeneic T cell proliferation. J Transl Med. 2014 May 30;12:151. doi: 10.1186/1479-5876-12-151. PMID: 24885059; PMCID: PMC4079621.
  41. Khan SU, Khan MU. Treatment of diabetic muscular hyperplasia with natural and nutritional supplements. Global Journal of Biotechnology and Biomaterial Science. 2022;8(1):001-008.
  42. Boes M, Meyer-Wentrup F. TLR3 triggering regulates PD-L1 (CD274) expression in human neuroblastoma cells. Cancer Lett. 2015 May 28;361(1):49-56. doi: 10.1016/j.canlet.2015.02.027. Epub 2015 Feb 16. PMID: 25697485.
  43. Coelho MA, de Carné Trécesson S, Rana S, Zecchin D, Moore C, Molina-Arcas M, East P, Spencer-Dene B, Nye E, Barnouin K, Snijders AP, Lai WS, Blackshear PJ, Downward J. Oncogenic RAS Signaling Promotes Tumor Immunoresistance by Stabilizing PD-L1 mRNA. Immunity. 2017 Dec 19;47(6):1083-1099.e6. doi: 10.1016/j.immuni.2017.11.016. Epub 2017 Dec 12. PMID: 29246442; PMCID: PMC5746170.
  44. Mao R, Tan X, Xiao Y, Wang X, Wei Z, Wang J, Wang X, Zhou H, Zhang L, Shi Y. Ubiquitin C-terminal hydrolase L1 promotes expression of programmed cell death-ligand 1 in non-small-cell lung cancer cells. Cancer Sci. 2020 Sep;111(9):3174-3183. doi: 10.1111/cas.14529. Epub 2020 Jul 6. PMID: 32539182; PMCID: PMC7469845.
  45. Qin G, Wang X, Ye S. NPM1 upregulates the transcrip-tion of PD-L1 and suppresses T cell activity in triple-negative breast cancer. Nat Commun. 2020;11(1):1669.
  46. Chen XM. MicroRNA signatures in liver diseases. World J Gastroenterol. 2009 Apr 14;15(14):1665-72. doi: 10.3748/wjg.15.1665. PMID: 19360909; PMCID: PMC2668771.
  47. Gong AY, Zhou R, Hu G, Li X, Splinter PL, O'Hara SP, LaRusso NF, Soukup GA, Dong H, Chen XM. MicroRNA-513 regulates B7-H1 translation and is involved in IFN-gamma-induced B7-H1 expression in cholangiocytes. J Immunol. 2009 Feb 1;182(3):1325-33. doi: 10.4049/jimmunol.182.3.1325. PMID: 19155478; PMCID: PMC2652126.
  48. Wang X, Li J, Dong K, Lin F, Long M, Ouyang Y, Wei J, Chen X, Weng Y, He T, Zhang H. Tumor suppressor miR-34a targets PD-L1 and functions as a potential immunotherapeutic target in acute myeloid leukemia. Cell Signal. 2015 Mar;27(3):443-52. doi: 10.1016/j.cellsig.2014.12.003. Epub 2014 Dec 10. PMID: 25499621.
  49. Khan SU, Khan MU. Recent Developments and Applications of Single-Cell RNA Sequencing Technology in Cell Classification. J Biomed Res Environ Sci. 2021 Dec 29;2(12):1283-1290. doi: 10.37871/jbres1383.
  50. Cortez MA, Ivan C, Valdecanas D, Wang X, Peltier HJ, Ye Y, Araujo L, Carbone DP, Shilo K, Giri DK, Kelnar K, Martin D, Komaki R, Gomez DR, Krishnan S, Calin GA, Bader AG, Welsh JW. PDL1 Regulation by p53 via miR-34. J Natl Cancer Inst. 2015 Nov 17;108(1):djv303. doi: 10.1093/jnci/djv303. PMID: 26577528; PMCID: PMC4862407.
  51. Chen L, Gibbons DL, Goswami S, Cortez MA, Ahn YH, Byers LA, Zhang X, Yi X, Dwyer D, Lin W, Diao L, Wang J, Roybal J, Patel M, Ungewiss C, Peng D, Antonia S, Mediavilla-Varela M, Robertson G, Suraokar M, Welsh JW, Erez B, Wistuba II, Chen L, Peng D, Wang S, Ullrich SE, Heymach JV, Kurie JM, Qin FX. Metastasis is regulated via microRNA-200/ZEB1 axis control of tumour cell PD-L1 expression and intratumoral immunosuppression. Nat Commun. 2014 Oct 28;5:5241. doi: 10.1038/ncomms6241. PMID: 25348003; PMCID: PMC4212319.
  52. Khan SU, Khan MU. The role of amino acid metabolic reprogramming in tumor development and immunotherapy. Biochemistry and Molecular Biology. 2022;7(1):6-12. doi: 10.11648/j.bmb.20220701.12.
  53. Fujita Y, Yagishita S, Hagiwara K, Yoshioka Y, Kosaka N, Takeshita F, Fujiwara T, Tsuta K, Nokihara H, Tamura T, Asamura H, Kawaishi M, Kuwano K, Ochiya T. The clinical relevance of the miR-197/CKS1B/STAT3-mediated PD-L1 network in chemoresistant non-small-cell lung cancer. Mol Ther. 2015 Apr;23(4):717-27. doi: 10.1038/mt.2015.10. Epub 2015 Jan 19. PMID: 25597412; PMCID: PMC4395779.
  54. Shao L, He Q, Wang J, He F, Lin S, Wu L, Gao Y, Ma W, Dong J, Yang X, Li F. MicroRNA-326 attenuates immune escape and prevents metastasis in lung adenocarcinoma by targeting PD-L1 and B7-H3. Cell Death Discov. 2021 Jun 15;7(1):145. doi: 10.1038/s41420-021-00527-8. PMID: 34131111; PMCID: PMC8206349.
  55. Xu S, Tao Z, Hai B, Liang H, Shi Y, Wang T, Song W, Chen Y, OuYang J, Chen J, Kong F, Dong Y, Jiang SW, Li W, Wang P, Yuan Z, Wan X, Wang C, Li W, Zhang X, Chen K. miR-424(322) reverses chemoresistance via T-cell immune response activation by blocking the PD-L1 immune checkpoint. Nat Commun. 2016 May 5;7:11406. doi: 10.1038/ncomms11406. PMID: 27147225; PMCID: PMC4858750.
  56. Zhao L, Yu H, Yi S, Peng X, Su P, Xiao Z, Liu R, Tang A, Li X, Liu F, Shen S. The tumor suppressor miR-138-5p targets PD-L1 in colorectal cancer. Oncotarget. 2016 Jul 19;7(29):45370-45384. doi: 10.18632/oncotarget.9659. PMID: 27248318; PMCID: PMC5216728.
  57. AUDRITO V, SERRA S, STINGI A, PD-L1 up-regulation in melanoma increases disease aggressiveness and is mediated through miR-17-5p .Oncotarget. 2017;8(9):15894-911.
  58. Khan SU, Khan MU. Advances in innate immune memory of macrophages. Explor Immunol. 2022;2:428–41. doi: 10.37349/ei.2022.00060.
  59. Cioffi M, Trabulo SM, Vallespinos M, Raj D, Kheir TB, Lin ML, Begum J, Baker AM, Amgheib A, Saif J, Perez M, Soriano J, Desco M, Gomez-Gaviro MV, Cusso L, Megias D, Aicher A, Heeschen C. The miR-25-93-106b cluster regulates tumor metastasis and immune evasion via modulation of CXCL12 and PD-L1. Oncotarget. 2017 Mar 28;8(13):21609-21625. doi: 10.18632/oncotarget.15450. PMID: 28423491; PMCID: PMC5400610.
  60. Lastwika KJ, Wilson W 3rd, Li QK, Norris J, Xu H, Ghazarian SR, Kitagawa H, Kawabata S, Taube JM, Yao S, Liu LN, Gills JJ, Dennis PA. Control of PD-L1 Expression by Oncogenic Activation of the AKT-mTOR Pathway in Non-Small Cell Lung Cancer. Cancer Res. 2016 Jan 15;76(2):227-38. doi: 10.1158/0008-5472.CAN-14-3362. Epub 2015 Dec 4. PMID: 26637667.
  61. Li CW, Lim SO, Xia W, Lee HH, Chan LC, Kuo CW, Khoo KH, Chang SS, Cha JH, Kim T, Hsu JL, Wu Y, Hsu JM, Yamaguchi H, Ding Q, Wang Y, Yao J, Lee CC, Wu HJ, Sahin AA, Allison JP, Yu D, Hortobagyi GN, Hung MC. Glycosylation and stabilization of programmed death ligand-1 suppresses T-cell activity. Nat Commun. 2016 Aug 30;7:12632. doi: 10.1038/ncomms12632. PMID: 27572267; PMCID: PMC5013604.
  62. McCubrey JA, Steelman LS, Bertrand FE, Davis NM, Sokolosky M, Abrams SL, Montalto G, D'Assoro AB, Libra M, Nicoletti F, Maestro R, Basecke J, Rakus D, Gizak A, Demidenko ZN, Cocco L, Martelli AM, Cervello M. GSK-3 as potential target for therapeutic intervention in cancer. Oncotarget. 2014 May 30;5(10):2881-911. doi: 10.18632/oncotarget.2037. PMID: 24931005; PMCID: PMC4102778.
  63. Zhang J, Bu X, Wang H, Zhu Y, Geng Y, Nihira NT, Tan Y, Ci Y, Wu F, Dai X, Guo J, Huang YH, Fan C, Ren S, Sun Y, Freeman GJ, Sicinski P, Wei W. Cyclin D-CDK4 kinase destabilizes PD-L1 via cullin 3-SPOP to control cancer immune surveillance. Nature. 2018 Jan 4;553(7686):91-95. doi: 10.1038/nature25015. Epub 2017 Nov 16. Erratum in: Nature. 2019 Jul;571(7766):E10. PMID: 29160310; PMCID: PMC5754234.
  64. Mezzadra R, Sun C, Jae LT. Identification of CMTM6 and CMTM4 as PD-L1 protein regulators. Nature. 2017;549(7670):106-110.
  65. Yang Y, Hsu JM, Sun L, Chan LC, Li CW, Hsu JL, Wei Y, Xia W, Hou J, Qiu Y, Hung MC. Palmitoylation stabilizes PD-L1 to promote breast tumor growth. Cell Res. 2019 Jan;29(1):83-86. doi: 10.1038/s41422-018-0124-5. Epub 2018 Dec 4. PMID: 30514902; PMCID: PMC6318320.
  66. Xu FF, Sun HM, Fang RP, Zhang L, Shi H, Wang X, Fu XL, Li XM, Shi XH, Wu Y, Ye K, Zhang WY, Ye LH. The modulation of PD-L1 induced by the oncogenic HBXIP for breast cancer growth. Acta Pharmacol Sin. 2022 Feb;43(2):429-445. doi: 10.1038/s41401-021-00631-6. Epub 2021 Apr 6. PMID: 33824459; PMCID: PMC8791967.
  67. Burr ML, Sparbier CE, Chan YC. CMTM6 main-tains the expression of PD-L1 and regulates anti-tumour immu-nity. Nature. 2017:549(7670):101-5.
  68. Maher CM, Thomas JD, Haas DA, Longen CG, Oyer HM, Tong JY, Kim FJ. Small-Molecule Sigma1 Modulator Induces Autophagic Degradation of PD-L1. Mol Cancer Res. 2018 Feb;16(2):243-255. doi: 10.1158/1541-7786.MCR-17-0166. Epub 2017 Nov 8. PMID: 29117944.
  69. Shang M, Yang H, Yang R, Chen T, Fu Y, Li Y, Fang X, Zhang K, Zhang J, Li H, Cao X, Gu J, Xiao J, Zhang Q, Liu X, Yu Q, Wang T. The folate cycle enzyme MTHFD2 induces cancer immune evasion through PD-L1 up-regulation. Nat Commun. 2021 Mar 29;12(1):1940. doi: 10.1038/s41467-021-22173-5. PMID: 33782411; PMCID: PMC8007798.
  70. Gao Y, Nihira NT, Bu X, Chu C, Zhang J, Kolodziejczyk A, Fan Y, Chan NT, Ma L, Liu J, Wang D, Dai X, Liu H, Ono M, Nakanishi A, Inuzuka H, North BJ, Huang YH, Sharma S, Geng Y, Xu W, Liu XS, Li L, Miki Y, Sicinski P, Freeman GJ, Wei W. Acetylation-dependent regulation of PD-L1 nuclear translocation dictates the efficacy of anti-PD-1 immunotherapy. Nat Cell Biol. 2020 Sep;22(9):1064-1075. doi: 10.1038/s41556-020-0562-4. Epub 2020 Aug 24. PMID: 32839551; PMCID: PMC7484128.
  71. Robainas M, Otano R, Bueno S, Ait-Oudhia S. Understanding the role of PD-L1/PD1 pathway blockade and autophagy in cancer therapy. Onco Targets Ther. 2017 Mar 23;10:1803-1807. doi: 10.2147/OTT.S132508. PMID: 28367063; PMCID: PMC5370068.
  72. Zhao Y, Wang XX, Wu W, Long H, Huang J, Wang Z, Li T, Tang S, Zhu B, Chen D. EZH2 regulates PD-L1 expression via HIF-1α in non-small cell lung cancer cells. Biochem Biophys Res Commun. 2019 Sep 17;517(2):201-209. doi: 10.1016/j.bbrc.2019.07.039. Epub 2019 Jul 19. PMID: 31331645.
  73. Haderk F, Schulz R, Iskar M, Cid LL, Worst T, Willmund KV, Schulz A, Warnken U, Seiler J, Benner A, Nessling M, Zenz T, Göbel M, Dürig J, Diederichs S, Paggetti J, Moussay E, Stilgenbauer S, Zapatka M, Lichter P, Seiffert M. Tumor-derived exosomes modulate PD-L1 expression in monocytes. Sci Immunol. 2017 Jul 28;2(13):eaah5509. doi: 10.1126/sciimmunol.aah5509. PMID: 28754746.
  74. Wei Y, Xiao X, Lao XM, Zheng L, Kuang DM. Immune landscape and therapeutic strategies: new insights into PD-L1 in tumors. Cell Mol Life Sci. 2021 Feb;78(3):867-887. doi: 10.1007/s00018-020-03637-1. Epub 2020 Sep 17. PMID: 32940722.
  75. Chen L, Han X. Anti-PD-1/PD-L1 therapy of human cancer: past, present, and future. J Clin Invest. 2015 Sep;125(9):3384-91. doi: 10.1172/JCI80011. Epub 2015 Sep 1. PMID: 26325035; PMCID: PMC4588282.
  76. Lee CM, Tannock IF. The distribution of the therapeutic monoclonal antibodies cetuximab and trastuzumab within solid tumors. BMC Cancer. 2010 Jun 3;10:255. doi: 10.1186/1471-2407-10-255. PMID: 20525277; PMCID: PMC2889896.
  77. Zarganes-Tzitzikas T, Konstantinidou M, Gao Y, Krzemien D, Zak K, Dubin G, Holak TA, Dömling A. Inhibitors of programmed cell death 1 (PD-1): a patent review (2010-2015). Expert Opin Ther Pat. 2016 Sep;26(9):973-7. doi: 10.1080/13543776.2016.1206527. Epub 2016 Jul 6. PMID: 27367741; PMCID: PMC5379636.
  78. Tan S, Zhang CW, Gao GF. Seeing is believing: anti-PD-1/PD-L1 monoclonal antibodies in action for checkpoint blockade tumor immunotherapy. Signal Transduct Target Ther. 2016 Nov 25;1:16029. doi: 10.1038/sigtrans.2016.29. PMID: 29263905; PMCID: PMC5661648.
  79. Park JJ, Thi EP, Carpio VH. Checkpoint inhibition through small molecule-induced internalization of programmed death-ligand 1. Nat Commun. 2021;12(1):1222.
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