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01-10-2018 | Review

Regulatory mechanisms of PD-L1 expression in cancer cells

Author: Yongyu Shi

Published in: Cancer Immunology, Immunotherapy | Issue 10/2018

Abstract

Immunotherapy targeting the PD-L1/PD-1 pathway using antibodies is effective in the clinical treatment of a multitude of cancers. This makes research of the regulatory mechanisms of PD-1 expression in cancer cells intriguing. PD-L1 expression can be categorized into inducible expression, attributed to extrinsic factors in the microenvironment, and constitutive expression, attributed to intrinsic cancer-driving gene alteration. The mechanisms of PD-L1 expression in cancer cells operate at multiple levels, including gene amplification, chromatin modification, transcription, posttranscription, translation and posttranslation. Moreover, some open questions in this field that need to be answered in future research are proposed. Studies of regulatory mechanisms of PD-L1 expression pave the way for the application of more effective approaches in the future of cancer immunotherapy.

Chen L, Han X (2015) Anti–PD-1/PD-L1 therapy of human cancer: past, present, and future. J Clin Investig 125:3384–3391. https://doi.org/10.1172/jci80011 CrossRefPubMed

Diem S, Hasan Ali O, Ackermann CJ, Bomze D, Koelzer VH, Jochum W, Speiser DE, Mertz KD, Flatz L (2018) Tumor infiltrating lymphocytes in lymph node metastases of stage III melanoma correspond to response and survival in nine patients treated with ipilimumab at the time of stage IV disease. Cancer Immunol Immunother CII. 67: 39–45. https://doi.org/10.1007/s00262-017-2061-4 CrossRefPubMed

Kansy BA, Concha-Benavente F, Srivastava RM et al (2017) PD-1 status in CD8(+) T cells associates with survival and anti-PD-1 therapeutic outcomes in head and neck cancer. Cancer Res 77:6353–6364. https://doi.org/10.1158/0008-5472.CAN-16-3167 CrossRefPubMed

Hellmann MD, Callahan MK, Awad MM et al (2018) Tumor mutational burden and efficacy of nivolumab monotherapy and in combination with ipilimumab in small-cell lung cancer. Cancer Cell 33:853–861e4. https://doi.org/10.1016/j.ccell.2018.04.001 CrossRefPubMed

Rittmeyer A, Barlesi F, Waterkamp D et al (2017) Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet 389:255–265. https://doi.org/10.1016/s0140-6736(16)32517-x CrossRefPubMed

Garcia-Diaz A, Shin DS, Moreno BH et al (2017) Interferon receptor signaling pathways regulating PD-L1 and PD-L2 expression. Cell Rep 19:1189–1201. https://doi.org/10.1016/j.celrep.2017.04.031 CrossRefPubMed

Lee SJ, Jang BC, Lee SW et al (2006) Interferon regulatory factor-1 is prerequisite to the constitutive expression and IFN-gamma-induced upregulation of B7-H1 (CD274). FEBS Lett. 580:755–762. https://doi.org/10.1016/j.febslet.2005.12.093 CrossRefPubMed

Li N, Wang J, Zhang N et al (2018) Cross-talk between TNF-alpha and IFN-gamma signaling in induction of B7-H1 expression in hepatocellular carcinoma cells. Cancer Immunol Immunother CII. 67: 271 – 83. https://doi.org/10.1007/s00262-017-2086-8 CrossRefPubMed

Concha-Benavente F, Srivastava RM, Trivedi S, Lei Y, Chandran U, Seethala RR, Freeman GJ, Ferris RL (2016) Identification of the cell-intrinsic and -extrinsic pathways downstream of EGFR and IFNgamma that induce PD-L1 expression in head and neck cancer. Cancer Res 76:1031–1043. https://doi.org/10.1158/0008-5472.CAN-15-2001 CrossRefPubMed

10.

Moon JW, Kong S-K, Kim BS et al (2017) IFNγ induces PD-L1 overexpression by JAK2/STAT1/IRF-1 signaling in EBV-positive gastric carcinoma. Sci Rep. https://doi.org/10.1038/s41598-017-18132-0 CrossRefPubMedPubMedCentral

11.

Liu J, Hamrouni A, Wolowiec D, Coiteux V, Kuliczkowski K, Hetuin D, Saudemont A, Quesnel B (2007) Plasma cells from multiple myeloma patients express B7-H1 (PD-L1) and increase expression after stimulation with IFN- and TLR ligands via a MyD88-, TRAF6-, and MEK-dependent pathway. Blood 110:296–304. https://doi.org/10.1182/blood-2006-10-051482 CrossRefPubMed

12.

Lim S-O, Li C-W, Xia W et al (2016) Deubiquitination and stabilization of PD-L1 by CSN5. Cancer Cell. https://doi.org/10.1016/j.ccell.2016.10.010 CrossRefPubMedPubMedCentral

13.

Wang X, Yang L, Huang F, Zhang Q, Liu S, Ma L, You Z (2017) Inflammatory cytokines IL-17 and TNF-alpha up-regulate PD-L1 expression in human prostate and colon cancer cells. Immunol Lett 184:7–14. https://doi.org/10.1016/j.imlet.2017.02.006 CrossRefPubMedPubMedCentral

14.

Okita R, Maeda A, Shimizu K, Nojima Y, Saisho S, Nakata M (2017) 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 CII. 66: 865 – 76. https://doi.org/10.1007/s00262-017-1986-y CrossRefPubMed

15.

Carbotti G, Barisione G, Airoldi I, Mezzanzanica D, Bagnoli M, Ferrero S, Petretto A, Fabbi M, Ferrini S (2015) IL-27 induces the expression of IDO and PD-L1 in human cancer cells. Oncotarget 6:43267–43280. https://doi.org/10.18632/oncotarget.6530 CrossRefPubMedPubMedCentral

16.

Quandt D, Jasinski-Bergner S, Muller U, Schulze B, Seliger B (2014) Synergistic effects of IL-4 and TNFalpha on the induction of B7-H1 in renal cell carcinoma cells inhibiting allogeneic T cell proliferation. J Transl Med 12:151. https://doi.org/10.1186/1479-5876-12-151 CrossRefPubMedPubMedCentral

17.

Yang L, Huang F, Mei J, Wang X, Zhang Q, Wang H, Xi M, You Z (2017) Posttranscriptional control of PD-L1 expression by 17beta-estradiol via PI3K/Akt signaling pathway in ERalpha-positive cancer cell lines. Int J Gynecol Cancer 27:196–205. https://doi.org/10.1097/IGC.0000000000000875 CrossRefPubMedPubMedCentral

18.

Boes M, Meyer-Wentrup F (2015) TLR3 triggering regulates PD-L1 (CD274) expression in human neuroblastoma cells. Cancer Lett 361:49–56. https://doi.org/10.1016/j.canlet.2015.02.027 CrossRefPubMed

19.

Qian Y, Deng J, Geng L et al (2008) TLR4 signaling induces B7-H1 expression through MAPK pathways in bladder cancer cells. Cancer Investig 26:816–821. https://doi.org/10.1080/07357900801941852 CrossRef

20.

Peng J, Hamanishi J, Matsumura N et al (2015) Chemotherapy induces programmed cell death-ligand 1 overexpression via the nuclear factor-kappaB to foster an immunosuppressive tumor microenvironment in ovarian cancer. Cancer Res 75:5034–5045. https://doi.org/10.1158/0008-5472.CAN-14-3098 CrossRefPubMed

21.

Casey SC, Tong L, Li Y et al (2016) MYC regulates the antitumor immune response through CD47 and PD-L1. Science 352:227–231. https://doi.org/10.1126/science.aac9935 CrossRefPubMedPubMedCentral

22.

Coelho MA, de Carne Trecesson S, Rana S et al (2017) Oncogenic RAS signaling promotes tumor immunoresistance by stabilizing PD-L1 mRNA. Immunity 47:1083–1099 e6. https://doi.org/10.1016/j.immuni.2017.11.016 CrossRefPubMedPubMedCentral

23.

Sumimoto H, Takano A, Teramoto K, Daigo Y (2016) RAS-mitogen-activated protein kinase signal is required for enhanced PD-L1 expression in human lung cancers. PloS One 11:e0166626. https://doi.org/10.1371/journal.pone.0166626 CrossRefPubMedPubMedCentral

24.

Akbay EA, Koyama S, Carretero J et al (2013) Activation of the PD-1 pathway contributes to immune escape in EGFR-driven lung tumors. Cancer Discov 3:1355–1363. https://doi.org/10.1158/2159-8290.CD-13-0310 CrossRefPubMed

25.

Ota K, Azuma K, Kawahara A et al (2015) Induction of PD-L1 expression by the EML4-ALK oncoprotein and downstream signaling pathways in non-small cell lung cancer. Clin Cancer Res 21:4014–4021. https://doi.org/10.1158/1078-0432.CCR-15-0016 CrossRefPubMed

26.

Parsa AT, Waldron JS, Panner A et al (2007) Loss of tumor suppressor PTEN function increases B7-H1 expression and immunoresistance in glioma. Nat Med 13:84–88. https://doi.org/10.1038/nm1517 CrossRefPubMed

27.

Xu C, Fillmore CM, Koyama S et al (2014) Loss of Lkb1 and Pten leads to lung squamous cell carcinoma with elevated PD-L1 expression. Cancer Cell 25:590–604. https://doi.org/10.1016/j.ccr.2014.03.033 CrossRefPubMedPubMedCentral

28.

Green MR, Monti S, Rodig SJ et al (2010) Integrative analysis reveals selective 9p24.1 amplification, increased PD-1 ligand expression, and further induction via JAK2 in nodular sclerosing Hodgkin lymphoma and primary mediastinal large B-cell lymphoma. Blood 116:3268–3277. https://doi.org/10.1182/blood-2010-05-282780 CrossRefPubMedPubMedCentral

29.

Cancer Genome Atlas Research N (2014) Comprehensive molecular characterization of gastric adenocarcinoma. Nature 513:202–209. https://doi.org/10.1038/nature13480 CrossRef

30.

Straub M, Drecoll E, Pfarr N et al (2016) CD274/PD-L1 gene amplification and PD-L1 protein expression are common events in squamous cell carcinoma of the oral cavity. Oncotarget 7:12024–12034. https://doi.org/10.18632/oncotarget.7593 CrossRefPubMedPubMedCentral

31.

George J, Saito M, Tsuta K et al (2017) Genomic amplification of CD274 (PD-L1) in small-cell lung cancer. Clin Cancer Res. 23: 1220–1226. https://doi.org/10.1158/1078-0432.CCR-16-1069 CrossRefPubMed

32.

Ikeda S, Okamoto T, Okano S et al (2016) PD-L1 is upregulated by simultaneous amplification of the PD-L1 and JAK2 genes in non-small cell lung cancer. J Thorac Oncol 11:62–71. https://doi.org/10.1016/j.jtho.2015.09.010 CrossRefPubMed

33.

Woods DM, Sodre AL, Villagra A, Sarnaik A, Sotomayor EM, Weber J (2015) HDAC inhibition upregulates PD-1 ligands in melanoma and augments immunotherapy with PD-1 blockade. Cancer Immunol Res 3:1375–1385. https://doi.org/10.1158/2326-6066.cir-15-0077-t CrossRefPubMedPubMedCentral

34.

Ellis L, Pan Y, Smyth GK et al (2008) Histone deacetylase inhibitor panobinostat induces clinical responses with associated alterations in gene expression profiles in cutaneous T-cell lymphoma. Clin Cancer Res 14:4500–4510. https://doi.org/10.1158/1078-0432.CCR-07-4262 CrossRefPubMed

35.

Mann BS, Johnson JR, Cohen MH, Justice R, Pazdur R (2007) FDA approval summary: vorinostat for treatment of advanced primary cutaneous T-cell lymphoma. Oncologist 12:1247–1252. https://doi.org/10.1634/theoncologist.12-10-1247 CrossRefPubMed

36.

West AC, Mattarollo SR, Shortt J, Cluse LA, Christiansen AJ, Smyth MJ, Johnstone RW (2013) An intact immune system is required for the anticancer activities of histone deacetylase inhibitors. Cancer Res 73:7265–7276. https://doi.org/10.1158/0008-5472.CAN-13-0890 CrossRefPubMed

37.

Lienlaf M, Perez-Villarroel P, Knox T et al (2016) Essential role of HDAC6 in the regulation of PD-L1 in melanoma. Mol Oncol 10:735–750. https://doi.org/10.1016/j.molonc.2015.12.012 CrossRefPubMedCentral

38.

Zhu H, Bengsch F, Svoronos N et al (2016) BET bromodomain inhibition promotes anti-tumor immunity by suppressing PD-L1 expression. Cell Rep 16:2829–2837. https://doi.org/10.1016/j.celrep.2016.08.032 CrossRefPubMedPubMedCentral

39.

Hogg SJ, Vervoort SJ, Deswal S et al (2017) BET-bromodomain inhibitors engage the host immune system and regulate expression of the immune checkpoint ligand PD-L1. Cell Rep 18:2162–2174. https://doi.org/10.1016/j.celrep.2017.02.011 CrossRefPubMedPubMedCentral

40.

Lu C, Paschall AV, Shi H, Savage N, Waller JL, Sabbatini ME, Oberlies NH, Pearce C, Liu K (2017) The MLL1-H3K4me3 axis-mediated PD-L1 expression and pancreatic cancer immune evasion. J Natl Cancer Inst. https://doi.org/10.1093/jnci/djw283 CrossRefPubMedPubMedCentral

41.

Green MR, Rodig S, Juszczynski P, Ouyang J, Sinha P, O’Donnell E, Neuberg D, Shipp MA (2012) Constitutive AP-1 activity and EBV infection induce PD-L1 in hodgkin lymphomas and posttransplant lymphoproliferative disorders: implications for targeted therapy. Clin Cancer Res 18:1611–1618. https://doi.org/10.1158/1078-0432.ccr-11-1942 CrossRefPubMedPubMedCentral

42.

Chen Y, Zhang J, Guo G et al (2009) Induced B7-H1 expression on human renal tubular epithelial cells by the sublytic terminal complement complex C5b-9. Mol Immunol 46:375–383. https://doi.org/10.1016/j.molimm.2008.10.026 CrossRefPubMed

43.

Viola JPB, Huang G, Wen Q, Zhao Y, Gao Q, Bai Y (2013) NF-κB plays a key role in inducing CD274 expression in human monocytes after lipopolysaccharide treatment. PloS One 8:e61602. https://doi.org/10.1371/journal.pone.0061602 CrossRef

44.

Maeda T, Hiraki M, Jin C et al (2018) MUC1-C induces PD-L1 and immune evasion in triple-negative breast cancer. Cancer Res 78:205–215. https://doi.org/10.1158/0008-5472.CAN-17-1636 CrossRefPubMed

45.

Chen H, Li C, Peng X, Zhou Z, Weinstein JN, Cancer Genome Atlas Research N, Liang H (2018) A pan-cancer analysis of enhancer expression in nearly 9000 patient samples. Cell 173:386 –386 99 e12. https://doi.org/10.1016/j.cell.2018.03.027 CrossRefPubMed

46.

Marzec M, Zhang Q, Goradia A et al (2008) Oncogenic kinase NPM/ALK induces through STAT3 expression of immunosuppressive protein CD274 (PD-L1, B7-H1). Proc Natl Acad Sci. 105:20852–20857. https://doi.org/10.1073/pnas.0810958105 CrossRefPubMed

47.

Atsaves V, Tsesmetzis N, Chioureas D et al (2017) PD-L1 is commonly expressed and transcriptionally regulated by STAT3 and MYC in ALK-negative anaplastic large-cell lymphoma. Leukemia 31:1633–1637. https://doi.org/10.1038/leu.2017.103 CrossRefPubMed

48.

Koh J, Jang JY, Keam B et al (2016) EML4-ALK enhances programmed cell death-ligand 1 expression in pulmonary adenocarcinoma via hypoxia-inducible factor (HIF)-1alpha and STAT3. Oncoimmunology 5:e1108514. https://doi.org/10.1080/2162402X.2015.1108514 CrossRefPubMed

49.

Kress TR, Sabo A, Amati B (2015) MYC: connecting selective transcriptional control to global RNA production. Nat Rev Cancer 15:593–607. https://doi.org/10.1038/nrc3984 CrossRefPubMed

50.

Durand-Panteix S, Farhat M, Youlyouz-Marfak I, Rouaud P, Ouk-Martin C, David A, Faumont N, Feuillard J, Jayat-Vignoles C (2012) B7-H1, which represses EBV-immortalized B cell killing by autologous T and NK cells, is oppositely regulated by c-Myc and EBV latency III program at both mRNA and secretory lysosome levels. J Immunol 189:181–90. https://doi.org/10.4049/jimmunol.1102277 CrossRefPubMed

51.

Noman MZ, Desantis G, Janji B, Hasmim M, Karray S, Dessen P, Bronte V, Chouaib S (2014) PD-L1 is a novel direct target of HIF-1alpha, and its blockade under hypoxia enhanced MDSC-mediated T cell activation. J Exp Med 211:781–790. https://doi.org/10.1084/jem.20131916 CrossRefPubMedPubMedCentral

52.

Ruf M, Moch H, Schraml P (2016) PD-L1 expression is regulated by hypoxia inducible factor in clear cell renal cell carcinoma. Int J Cancer J international du cancer 139:396–403. https://doi.org/10.1002/ijc.30077 CrossRef

53.

Kataoka K, Shiraishi Y, Takeda Y et al (2016) Aberrant PD-L1 expression through 3′-UTR disruption in multiple cancers. Nature 534:402–406. https://doi.org/10.1038/nature18294 CrossRefPubMed

54.

Wang Q, Lin W, Tang X, Li S, Guo L, Lin Y, Kwok H (2017) The roles of microRNAs in regulating the expression of PD-1/PD-L1 immune checkpoint. Int J Mol Sci 18:2540. https://doi.org/10.3390/ijms18122540 CrossRefPubMedCentral

55.

Kao SC, Cheng YY, Williams M et al (2017) Tumor suppressor microRNAs contribute to the regulation of PD-L1 expression in malignant pleural mesothelioma. J Thoracic Oncol 12:1421–1433. https://doi.org/10.1016/j.jtho.2017.05.024 CrossRef

56.

Cioffi M, Trabulo SM, Vallespinos M et al (2017) The miR-25-93-106b cluster regulates tumor metastasis and immune evasion via modulation of CXCL12 and PD-L1. Oncotarget 8:21609–21625. https://doi.org/10.18632/oncotarget.15450 CrossRefPubMedPubMedCentral

57.

Jia L, Xi Q, Wang H et al (2017) miR-142-5p regulates tumor cell PD-L1 expression and enhances anti-tumor immunity. Biochem Biophys Res Commun 488:425–431. https://doi.org/10.1016/j.bbrc.2017.05.074 CrossRefPubMed

58.

Audrito V, Serra S, Stingi A et al (2017) PD-L1 up-regulation in melanoma increases disease aggressiveness and is mediated through miR-17-5p. Oncotarget 8:15894–15911. https://doi.org/10.18632/oncotarget.15213 CrossRefPubMedPubMedCentral

59.

Wang Y, Wang D, Xie G, Yin Y, Zhao E, Tao K, Li R (2017) MicroRNA-152 regulates immune response via targeting B7-H1 in gastric carcinoma. Oncotarget 8:28125–28134. https://doi.org/10.18632/oncotarget.15924 CrossRefPubMedPubMedCentral

60.

Xu S, Tao Z, Hai B et al (2016) miR-424(322) reverses chemoresistance via T-cell immune response activation by blocking the PD-L1 immune checkpoint. Nat Commun 7:11406. https://doi.org/10.1038/ncomms11406 CrossRefPubMedPubMedCentral

61.

Wang X, Li J, Dong K et al (2015) Tumor suppressor miR-34a targets PD-L1 and functions as a potential immunotherapeutic target in acute myeloid leukemia. Cell Signal 27:443–452. https://doi.org/10.1016/j.cellsig.2014.12.003 CrossRefPubMed

62.

Gong AY, Zhou R, Hu G et al (2009) MicroRNA-513 regulates B7-H1 translation and is involved in IFN-gamma-induced B7-H1 expression in cholangiocytes. J Immunol 182:1325–1333CrossRef

63.

Lastwika KJ, Wilson W IIIrd, Li QK et al (2016) Control of PD-L1 expression by oncogenic activation of the AKT-mTOR pathway in non-small cell lung cancer. Cancer Res 76:227–238. https://doi.org/10.1158/0008-5472.CAN-14-3362 CrossRefPubMed

64.

Clague MJ, Urbe S (2010) Ubiquitin: same molecule, different degradation pathways. Cell 143:682–685. https://doi.org/10.1016/j.cell.2010.11.012 CrossRefPubMed

65.

Zhang J, Bu X, Wang H et al (2017) Cyclin D-CDK4 kinase destabilizes PD-L1 via Cul3(SPOP) to control cancer immune surveillance. Nature. https://doi.org/10.1038/nature25015 CrossRefPubMedPubMedCentral

66.

Li C-W, Lim S-O, Xia W et al (2016) Glycosylation and stabilization of programmed death ligand-1 suppresses T-cell activity. Nat Commun 7:12632. https://doi.org/10.1038/ncomms12632 CrossRefPubMedPubMedCentral

67.

Jiao S, Xia W, Yamaguchi H et al (2017) PARP inhibitor upregulates PD-L1 expression and enhances cancer-associated immunosuppression. Clin Cancer Res. 23: 3711–3720. https://doi.org/10.1158/1078-0432.CCR-16-3215 CrossRefPubMedPubMedCentral

68.

Mezzadra R, Sun C, Jae LT et al (2017) Identification of CMTM6 and CMTM4 as PD-L1 protein regulators. Nature 549:106–110. https://doi.org/10.1038/nature23669 CrossRefPubMed

69.

Burr ML, Sparbier CE, Chan YC et al (2017) CMTM6 maintains the expression of PD-L1 and regulates anti-tumour immunity. Nature 549:101–105. https://doi.org/10.1038/nature23643 CrossRefPubMedPubMedCentral

70.

Maher CM, Thomas JD, Haas DA, Longen CG, Oyer HM, Tong JY, Kim FJ (2018) Small-molecule sigma1 modulator induces autophagic degradation of PD-L1. Mol Cancer Res MCR 16:243–255. https://doi.org/10.1158/1541-7786.MCR-17-0166 CrossRefPubMed

71.

Berthon C, Raffoux E, Thomas X et al (2016) Bromodomain inhibitor OTX015 in patients with acute leukaemia: a dose-escalation, phase 1 study. Lancet Haematol 3:e186–e195. https://doi.org/10.1016/s2352-3026(15)00247-1 CrossRefPubMed

72.

Amorim S, Stathis A, Gleeson M et al (2016) Bromodomain inhibitor OTX015 in patients with lymphoma or multiple myeloma: a dose-escalation, open-label, pharmacokinetic, phase 1 study. Lancet Haematol 3:e196–e204. https://doi.org/10.1016/s2352-3026(16)00021-1 CrossRefPubMed

73.

Choueiri TK, Escudier B, Powles T et al (2016) Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial. Lancet Oncol 17:917–927. https://doi.org/10.1016/s1470-2045(16)30107-3 CrossRefPubMed

74.

Powles T, Lackner MR, Oudard S et al (2016) Randomized open-label phase II trial of apitolisib (GDC-0980), a novel inhibitor of the PI3K/mammalian target of rapamycin pathway, versus everolimus in patients with metastatic renal cell carcinoma. J Clin Oncol 34:1660–1668. https://doi.org/10.1200/JCO.2015.64.8808 CrossRefPubMedPubMedCentral

75.

Shin DS, Zaretsky JM, Escuin-Ordinas H et al (2017) Primary resistance to PD-1 blockade mediated by JAK1/2 mutations. Cancer Discov 7:188–201. https://doi.org/10.1158/2159-8290.CD-16-1223 CrossRefPubMed

76.

Zaretsky JM, Garcia-Diaz A, Shin DS et al (2016) Mutations associated with acquired resistance to PD-1 blockade in melanoma. N Engl J Med 375:819–829. https://doi.org/10.1056/NEJMoa1604958 CrossRefPubMedPubMedCentral

77.

Gao J, Shi LZ, Zhao H et al (2016) Loss of IFN-gamma pathway genes in tumor cells as a mechanism of resistance to anti-CTLA-4 therapy. Cell 167:397–404 e9. https://doi.org/10.1016/j.cell.2016.08.069 CrossRefPubMedPubMedCentral

78.

Kearney CJ, Vervoort SJ, Hogg SJ et al (2018) Tumor immune evasion arises through loss of TNF sensitivity. Sci Immunol. https://doi.org/10.1126/sciimmunol.aar3451 CrossRefPubMed

79.

Manguso RT, Pope HW, Zimmer MD et al (2017) In vivo CRISPR screening identifies Ptpn2 as a cancer immunotherapy target. Nature 547:413–418. https://doi.org/10.1038/nature23270 CrossRefPubMedPubMedCentral

Title: Regulatory mechanisms of PD-L1 expression in cancer cells
Author: Yongyu Shi
Publication date: 01-10-2018
Publisher: Springer Berlin Heidelberg
Published in: Cancer Immunology, Immunotherapy / Issue 10/2018
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-018-2226-9

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