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Original Research

The immune checkpoint protein PD-L1 induces and maintains regulatory T cells in glioblastoma

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Article: e1448329 | Received 23 Oct 2017, Accepted 28 Feb 2018, Published online: 25 Apr 2018

References

  • Chinot OL, Wick W, Mason W, Henriksson R, Saran F, Nishikawa R, Carpentier AF, Hoang-Xuan K, Kavan P, Cernea D, et al. Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma. N Engl J Med. 2014;370:709–22. doi:10.1056/NEJMoa1308345. PMID:24552318.
  • Gilbert MR, Dignam JJ, Armstrong TS, Wefel JS, Blumenthal DT, Vogelbaum MA, Colman H, Chakravarti A, Pugh S, Won M, et al. A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med. 2014;370:699–708. doi:10.1056/NEJMoa1308573. PMID:24552317.
  • Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 2009; 10:459–66. doi:10.1016/S1470-2045(09)70025-7. PMID:19269895.
  • Tan AC, Heimberger AB, Khasraw M. Immune Checkpoint Inhibitors in Gliomas. Curr Oncol Rep. 2017;19:23. doi:10.1007/s11912-017-0586-5. PMID:28303490.
  • Bloch O. Immunotherapy for malignant gliomas. Cancer Treat Res 2015; 163:143–58. doi:10.1007/978-3-319-12048-5_9. PMID:25468230.
  • Dummer W, Niethammer AG, Baccala R, Lawson BR, Wagner N, Reisfeld RA, Theofilopoulos AN. T cell homeostatic proliferation elicits effective antitumor autoimmunity. J Clin Invest. 2002;110:185–92. doi:10.1172/JCI0215175. PMID:12122110.
  • Albesiano E, Han JE, Lim M. Mechanisms of local immunoresistance in glioma. Neurosurg Clin N Am. 2010;21:17–29. doi:10.1016/j.nec.2009.08.008. PMID:19944963.
  • Heimberger AB, Abou-Ghazal M, Reina-Ortiz C, Yang DS, Sun W, Qiao W, Hiraoka N, Fuller GN. Incidence and prognostic impact of FoxP3+ regulatory T cells in human gliomas. Clin Cancer Res. 2008;14:5166–72. doi:10.1158/1078-0432.CCR-08-0320. PMID:18698034.
  • Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol. 2003;4:330–6. doi:10.1038/ni904. PMID:12612578.
  • Liau LM, Prins RM, Kiertscher SM, Odesa SK, Kremen TJ, Giovannone AJ, Lin JW, Chute DJ, Mischel PS, Cloughesy TF, et al. Dendritic cell vaccination in glioblastoma patients induces systemic and intracranial T-cell responses modulated by the local central nervous system tumor microenvironment. Clin Cancer Res. 2005;11:5515–25. doi:10.1158/1078-0432.CCR-05-0464. PMID:16061868.
  • Fecci PE, Mitchell DA, Whitesides JF, Xie W, Friedman AH, Archer GE, Herndon JE, 2nd, Bigner DD, Dranoff G, Sampson JH. Increased regulatory T-cell fraction amidst a diminished CD4 compartment explains cellular immune defects in patients with malignant glioma. Cancer Res. 2006;66:3294–302. doi:10.1158/0008-5472.CAN-05-3773. PMID:16540683.
  • Fecci PE, Ochiai H, Mitchell DA, Grossi PM, Sweeney AE, Archer GE, Cummings T, Allison JP, Bigner DD, Sampson JH. Systemic CTLA-4 blockade ameliorates glioma-induced changes to the CD4+ T cell compartment without affecting regulatory T-cell function. Clin Cancer Res. 2007;13:2158–67. doi:10.1158/1078-0432.CCR-06-2070. PMID:17404100.
  • Crane CA, Ahn BJ, Han SJ, Parsa AT. Soluble factors secreted by glioblastoma cell lines facilitate recruitment, survival, and expansion of regulatory T cells: implications for immunotherapy. Neuro Oncol. 2012;14:584–95. doi:10.1093/neuonc/nos014. PMID:22406925.
  • Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, Roche PC, Lu J, Zhu G, Tamada K, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med. 2002;8:793–800. doi:10.1038/nm730. PMID:12091876.
  • Wintterle S, Schreiner B, Mitsdoerffer M, Schneider D, Chen L, Meyermann R, Weller M, Wiendl H. Expression of the B7-related molecule B7-H1 by glioma cells: a potential mechanism of immune paralysis. Cancer Res. 2003;63:7462–7. PMID:14612546.
  • Parsa AT, Waldron JS, Panner A, Crane CA, Parney IF, Barry JJ, Cachola KE, Murray JC, Tihan T, Jensen MC, et al. Loss of tumor suppressor PTEN function increases B7-H1 expression and immunoresistance in glioma. Nat Med. 2007;13:84–8. doi:10.1038/nm1517. PMID:17159987.
  • Kuang DM, Zhao Q, Peng C, Xu J, Zhang JP, Wu C, Zheng L. Activated monocytes in peritumoral stroma of hepatocellular carcinoma foster immune privilege and disease progression through PD-L1. J Exp Med. 2009;206:1327–37. doi:10.1084/jem.20082173. PMID:19451266.
  • Rodrigues JC, Gonzalez GC, Zhang L, Ibrahim G, Kelly JJ, Gustafson MP, Lin Y, Dietz AB, Forsyth PA, Yong VW, et al. Normal human monocytes exposed to glioma cells acquire myeloid-derived suppressor cell-like properties. Neuro Oncol. 2010;12:351–65. doi:10.1093/neuonc/nop023. PMID:20308313.
  • Dziurzynski K, Wei J, Qiao W, Hatiboglu MA, Kong LY, Wu A, Wang Y, Cahill D, Levine N, Prabhu S, et al. Glioma-associated cytomegalovirus mediates subversion of the monocyte lineage to a tumor propagating phenotype. Clin Cancer Res. 2011;17:4642–9. doi:10.1158/1078-0432.CCR-11-0414. PMID:21490182.
  • Bloch O, Crane CA, Kaur R, Safaee M, Rutkowski MJ, Parsa AT. Gliomas promote immunosuppression through induction of B7-H1 expression in tumor-associated macrophages. Clin Cancer Res. 2013;19:3165–75. doi:10.1158/1078-0432.CCR-12-3314. PMID:23613317.
  • Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, Fitz LJ, Malenkovich N, Okazaki T, Byrne MC, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med. 2000;192:1027–34. doi:10.1084/jem.192.7.1027. PMID:11015443.
  • Bloch O, Lim M, Sughrue ME, Komotar RJ, Abrahams JM, O'Rourke DM, D'Ambrosio A, Bruce JN, Parsa AT. Autologous Heat Shock Protein Peptide Vaccination for Newly Diagnosed Glioblastoma: Impact of Peripheral PD-L1 Expression on Response to Therapy. Clin Cancer Res. 2017;23:3575–84. doi:10.1158/1078-0432.CCR-16-1369. PMID:28193626.
  • Asano T, Meguri Y, Yoshioka T, Kishi Y, Iwamoto M, Nakamura M, Sando Y, Yagita H, Koreth J, Kim HT, et al. PD-1 modulates regulatory T-cell homeostasis during low-dose interleukin-2 therapy. Blood. 2017;129:2186–97. doi:10.1182/blood-2016-09-741629. PMID:28151427.
  • Syed Khaja AS, Toor SM, El Salhat H, Ali BR, Elkord E. Intratumoral FoxP3+Helios+ Regulatory T Cells Upregulating Immunosuppressive Molecules Are Expanded in Human Colorectal Cancer. Front Immunol. 2017;8:619. doi:10.3389/fimmu.2017.00619. PMID:28603527.
  • Francisco LM, Salinas VH, Brown KE, Vanguri VK, Freeman GJ, Kuchroo VK, Sharpe AH. PD-L1 regulates the development, maintenance, and function of induced regulatory T cells. J Exp Med. 2009;206:3015–29. doi:10.1084/jem.20090847. PMID:20008522.
  • Lowther DE, Goods BA, Lucca LE, Lerner BA, Raddassi K, van Dijk D, Hernandez AL, Duan X, Gunel M, Coric V, et al. PD-1 marks dysfunctional regulatory T cells in malignant gliomas. JCI Insight. 2016;1(5):e85935. doi:10.1172/jci.insight.85935. PMID:27182555.
  • Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, Jacobsen A, Byrne CJ, Heuer ML, Larsson E, et al. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2012;2:401–4. doi:10.1158/2159-8290.CD-12-0095. PMID:22588877.
  • Gao J, Aksoy BA, Dogrusoz U, Dresdner G, Gross B, Sumer SO, Sun Y, Jacobsen A, Sinha R, Larsson E, et al. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal. 2013;6:pl1. doi:10.1126/scisignal.2004088. PMID:23550210.
  • Ganesan AP, Johansson M, Ruffell B, Yagui-Beltran A, Lau J, Jablons DM, Coussens LM. Tumor-infiltrating regulatory T cells inhibit endogenous cytotoxic T cell responses to lung adenocarcinoma. J Immunol. 2013;191:2009–17. doi:10.4049/jimmunol.1301317. PMID:23851682.
  • Li Z, Dong P, Ren M, Song Y, Qian X, Yang Y, Li S, Zhang X, Liu F. PD-L1 Expression Is Associated with Tumor FOXP3(+) Regulatory T-Cell Infiltration of Breast Cancer and Poor Prognosis of Patient. J Cancer. 2016;7:784–93. doi:10.7150/jca.14549. PMID:27162536.
  • Que Y, Xiao W, Guan YX, Liang Y, Yan SM, Chen HY, Li QQ, Xu BS, Zhou ZW, Zhang X. PD-L1 Expression Is Associated with FOXP3+ Regulatory T-Cell Infiltration of Soft Tissue Sarcoma and Poor Patient Prognosis. J Cancer. 2017;8:2018–25. doi:10.7150/jca.18683. PMID:28819402.
  • Chen X, Fosco D, Kline DE, Meng L, Nishi S, Savage PA, Kline J. PD-1 regulates extrathymic regulatory T-cell differentiation. Eur J Immunol. 2014;44:2603–16. doi:10.1002/eji.201344423. PMID:24975127.
  • Wainwright DA, Sengupta S, Han Y, Lesniak MS. Thymus-derived rather than tumor-induced regulatory T cells predominate in brain tumors. Neuro Oncol. 2011;13:1308–23. doi:10.1093/neuonc/nor134. PMID:21908444.
  • Fong B, Jin R, Wang X, Safaee M, Lisiero DN, Yang I, Li G, Liau LM, Prins RM. Monitoring of regulatory T cell frequencies and expression of CTLA-4 on T cells, before and after DC vaccination, can predict survival in GBM patients. PLoS One. 2012;7:e32614. doi:10.1371/journal.pone.0032614. PMID:22485134.
  • Jacobs JF, Idema AJ, Bol KF, Nierkens S, Grauer OM, Wesseling P, Grotenhuis JA, Hoogerbrugge PM, de Vries IJ, Adema GJ. Regulatory T cells and the PD-L1/PD-1 pathway mediate immune suppression in malignant human brain tumors. Neuro Oncol. 2009;11:394–402. doi:10.1215/15228517-2008-104. PMID:19028999.
  • Zhang Y, Huang S, Gong D, Qin Y, Shen Q. Programmed death-1 upregulation is correlated with dysfunction of tumor-infiltrating CD8+ T lymphocytes in human non-small cell lung cancer. Cell Mol Immunol. 2010;7:389–95. doi:10.1038/cmi.2010.28. PMID:20514052.
  • Sauer S, Bruno L, Hertweck A, Finlay D, Leleu M, Spivakov M, Knight ZA, Cobb BS, Cantrell D, O'Connor E, et al. T cell receptor signaling controls Foxp3 expression via PI3K, Akt, and mTOR. Proc Natl Acad Sci U S A. 2008;105:7797–802. doi:10.1073/pnas.0800928105. PMID:18509048.
  • Haxhinasto S, Mathis D, Benoist C. The AKT-mTOR axis regulates de novo differentiation of CD4+Foxp3+ cells. J Exp Med. 2008;205:565–74. doi:10.1084/jem.20071477. PMID:18283119.
  • Li MO, Rudensky AY. T cell receptor signalling in the control of regulatory T cell differentiation and function. Nat Rev Immunol. 2016;16:220–33. doi:10.1038/nri.2016.26. PMID:27026074.
  • Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, Chow LQ, Vokes EE, Felip E, Holgado E, et al. Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N Engl J Med. 2015;373:1627–39. doi:10.1056/NEJMoa1507643. PMID:26412456.
  • Brahmer J, Reckamp KL, Baas P, Crino L, Eberhardt WE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holgado E, et al. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med. 2015;373:123–35. doi:10.1056/NEJMoa1504627. PMID:26028407.
  • Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, Schadendorf D, Dummer R, Smylie M, Rutkowski P, et al. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med. 2015;373:23–34. doi:10.1056/NEJMoa1504030. PMID:26027431.
  • Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S, Tykodi SS, Sosman JA, Procopio G, Plimack ER, et al. Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med. 2015;373:1803–13. doi:10.1056/NEJMoa1510665. PMID:26406148.
  • Weber JS, D'Angelo SP, Minor D, Hodi FS, Gutzmer R, Neyns B, Hoeller C, Khushalani NI, Miller WH, Jr., Lao CD, et al. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2015;16:375–84. doi:10.1016/S1470-2045(15)70076-8. PMID:25795410.
  • Kaplan EL, Meier P. Nonparametric Estimation from Incomplete Observations. Journal of the American Statistical Association. 1958;53:457–81. doi:10.1080/01621459.1958.10501452.

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