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Article

Downregulation of PD‑L1 via amide analogues of brefelamide: Alternatives to antibody‑based cancer immunotherapy

  • Authors:
    • Jing Zhang
    • Osamu Yamada
    • Shinya Kida
    • Shinya Murase
    • Toshio Hattori
    • Yoshiteru Oshima
    • Haruhisa Kikuchi
  • View Affiliations / Copyright

    Affiliations: Research and Development Center, FUSO Pharmaceutical Industries, Ltd., Osaka 536‑8523, Japan, Department of Health Science and Social Welfare, Kibi International University, Takahashi, Okayama 716‑8508, Japan, Laboratory of Natural Products Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi 980‑8578, Japan
  • Pages: 3150-3158
    |
    Published online on: February 26, 2020
       https://doi.org/10.3892/etm.2020.8553
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Abstract

The therapeutic blockade of immune checkpoint has emerged as an effective treatment option for a broad range of tumors. However, the objective tumor response is still limited to a small number of cases and tumor types. The full utility of monoclonal antibody (mAb)‑based treatment is hindered by several inherent limitations. Thus, there is an urgent requirement to explore alternative modalities targeting the same pathways. In the present study, two amide analogues of brefelamide, TPFS‑201 and TPFS‑202, were identified as small molecular immune checkpoint inhibitors, as they downregulated PD‑L1 expression in tumor cells. PD‑L1 was suppressed in cancer cells treated with TPFD compounds at both mRNA and protein levels, as detected by reverse transcription quantitative PCR and flow cytometric analysis, respectively. Reporter assays using a PD‑L1 promoter luciferase construct confirmed the transcriptional inhibition of PD‑L1 by TPFS compunds. TPFS compound‑mediated PD‑L1 downregulation in cancer cells consequently restored T cell activity, as identified by the reduction of apoptosis and an increase in interleukin‑2 promoter activity in Jurkat T cells, which were co‑cultured with TPFS compound‑treated A549 cells. TPFS compound‑mediated PD‑L1 inhibition was partially abolished by the disruption of the putative transcriptional co‑activator with PDZ (TAZ)/TEA domain (TEAD)‑binding motif in the PD‑L1 promoter. The inhibitory effect of TPFS compounds on PD‑L1 was markedly inhibited in mouse cell lines, which is consistent with previous research demonstrating that PD‑L1 regulation by TAZ is not conserved in mice due to distinct promoter sequences flanking the TAZ/TEAD‑binding motif. Together, the data of the current study indicated the potential utility of the brefelamide amide analogues as small molecule immune checkpoint inhibitors, thereby providing therapeutic alternatives, which could be used as monotherapy or in combination with mAbs‑based treatment.
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1 

Zajac AJ, Blattman JN, Murali-Krishna K, Sourdive DJ, Suresh M, Altman JD and Ahmed R: Viral immune evasion due to persistence of activated T cells without effector function. J Exp Med. 188:2205–2213. 1998.PubMed/NCBI View Article : Google Scholar

2 

Gallimore A, Glithero A, Godkin A, Tissot AC, Plückthun A, Elliott T, Hengartner H and Zinkernagel R: Induction and exhaustion of lymphocytic choriomeningitis virus-specific cytotoxic T lymphocytes visualized using soluble tetrameric major histocompatibility complex class I-peptide complexes. J Exp Med. 187:1383–1393. 1998.PubMed/NCBI View Article : Google Scholar

3 

Fuller MJ, Khanolkar A, Tebo AE and Zajac AJ: Maintenance, loss, and resurgence of T cell responses during acute, protracted, and chronic viral infections. J Immunol. 172:4204–4214. 2004.PubMed/NCBI View Article : Google Scholar

4 

Wherry EJ: T cell exhausion. Nat Immunol. 12:492–499. 2011.PubMed/NCBI View Article : Google Scholar

5 

Doering TA, Crawford A, Angelosanto JM, Paley MA, Ziegler CG and Wherry EJ: Network and analysis reveals centrally connected genes and pathways involved in CD8+ T cell exhaustion versus memory. Immunity. 37:1130–1144. 2012.PubMed/NCBI View Article : Google Scholar

6 

Schietinger A and Greenberg PD: Tolerance and exhaustion: Defining mechanisms of T cell dysfunction. Trends Immunol. 35:51–60. 2014.PubMed/NCBI View Article : Google Scholar

7 

Butte MJ, Keir ME, Phamduy TB, Sharpe AH and Freeman GJ: Programmed death-1ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses. Immunity. 27:111–122. 2007.PubMed/NCBI View Article : Google Scholar

8 

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. 192:1027–1034. 2000.PubMed/NCBI View Article : Google Scholar

9 

Couzin-Frankel J: Breakthrough of the year 2013. Cancer immunotherapy. Science. 342:1432–1433. 2013.PubMed/NCBI View Article : Google Scholar

10 

Butt AQ and Mills KH: Immunosuppressive networks and checkpoints controlling antitumor immunity and their blockade in the development of cancer immunotherapeutics and vaccines. Oncogene. 33:4623–4631. 2014.PubMed/NCBI View Article : Google Scholar

11 

Merelli B, Massi D, Cattaneo L and Mandalà M: Targeting the PD1/PD-L1 axis in melanoma: Biological rationale, clinical challenges and opportunities. Crit Rev Oncol Hematol. 89:140–165. 2014.PubMed/NCBI View Article : Google Scholar

12 

Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, Patnaik A, Aggarwal C, Gubens M, Horn L, et al: Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 372:2018–2028. 2015.PubMed/NCBI View Article : Google Scholar

13 

Rosenberg JE, Hoffman-Censits J, Powles T, van der Heijden MS, Balar AV, Necchi A, Dawson N, O'Donnell PH, Balmanoukian A, Loriot Y, et al: Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: A single-arm, multicentre, phase 2 trial. Lancet. 387:1909–1920. 2016.PubMed/NCBI View Article : Google Scholar

14 

Ansell SM, Lesokhin AM, Borrello I, Halwani A, Scott EC, Gutierrez M, Schuster SJ, Millenson MM, Cattry D, Freeman GJ, et al: PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N Engl J Med. 372:311–319. 2015. View Article : Google Scholar

15 

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. 373:1803–1813. 2015.PubMed/NCBI View Article : Google Scholar

16 

Caspi RR: Immunotherapy of autoimmunity and cancer: The penalty for success. Nat Rev Immunol. 8:970–976. 2008.PubMed/NCBI View Article : Google Scholar

17 

Amos SM, Duong CP, Westwood JA, Ritchie DS, Junghans RP, Darcy PK and Kershaw MH: Autoimmunity associated with immunotherapy of cancer. Blood. 118:499–509. 2011.PubMed/NCBI View Article : Google Scholar

18 

Lin DY, Tanaka Y, Iwasaki M, Gittis AG, Su HP, Mikami B, Okazaki T, Honjo T, Minato N and Garboczi DN: The PD-1/PD-L1 complex resembles the antigen-binding Fv domains of antibodies and T cell receptors. Pro Natl Acad Sci USA. 105:3011–3016. 2008.PubMed/NCBI View Article : Google Scholar

19 

Dong H, Zhu G, Tamada K and Chen L: B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat Med. 5:1365–1369. 1999.PubMed/NCBI View Article : Google Scholar

20 

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. 192:1027–1034. 2000.PubMed/NCBI View Article : Google Scholar

21 

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. 8:793–800. 2002.PubMed/NCBI View Article : Google Scholar

22 

Ding H, Wu X and Gao W: PD-L1 is expressed by human renal tubular epithelial cells and suppresses T cell cytokine synthesis. Clin Immunol. 115:184–191. 2005.PubMed/NCBI View Article : Google Scholar

23 

Yang CY, Lin MW, Chang YL, Wu CT and Yang PC: Programmed cell death-ligand 1 expression in surgically resected stage I pulmonary adenocarcinoma and its correlation with driver mutations and clinical outcomes. Eur J Cancer. 50:1361–1369. 2014.PubMed/NCBI View Article : Google Scholar

24 

Gao Q, Wang XY, Qiu SJ, Yamato I, Sho M, Nakajima Y, Zhou J, Li BZ, Shi YH, Xiao YS, et al: Overexpression of PD-L1 significantly associates with tumor aggressiveness and postoperative recurrence in human hepatocellular carcinoma. Clin Cancer Res. 15:971–979. 2009.PubMed/NCBI View Article : Google Scholar

25 

Hino R, Kabashima K, Kato Y, Yagi H, Nakamura M, Honjo T, Okazaki T and Tokura Y: Tumor cell expression of programmed cell death-1 ligand 1 is a prognostic factor for malignant melanoma. Cancer. 116:1757–1766. 2010.PubMed/NCBI View Article : Google Scholar

26 

Kikuchi H, Saito Y, Sekiya J, Okano Y, Saito M, Nakahata N, Kubohara Y and Oshima Y: Isolation and synthesis of a new aromatic compound, brefelamide, from dictyostelium cellular slime molds and its inhibitory effect on the proliferation of astrocytoma cells. J Org Chem. 70:8854–8858. 2005.PubMed/NCBI View Article : Google Scholar

27 

Honma S, Saito M, Kikuchi H, Saito Y, OshimaY Nakahata N and Yoshida M: A reduction of epidermal growth factor receptor is involved in brefelamide induced inhibition of phosphorylation of ERK in human astrocytoma cells. Eur J Pharmacol. 616:38–42. 2009.PubMed/NCBI View Article : Google Scholar

28 

Zhang J, Yamada O, Kida S, Matsushita Y, Murase S, Hattori T, Kubohara Y, Kikuchi H and Oshima Y: Identification of brefelamide as a novel inhibitor of osteopontin that suppresses invasion of A549 lung cancer cells. Oncol Rep. 36:2357–2364. 2016.PubMed/NCBI View Article : Google Scholar

29 

Janse van Rensburg HJ, Azad T, Ling M, Hao Y, Snetsinger B, Khanal P, Minassian LM, Graham CH, Rauh MJ and Yang X: The hippo pathway component TAZ promotes immune evasion in human cancer through PD-L1. Cancer Res. 78:1457–1470. 2018.PubMed/NCBI View Article : Google Scholar

30 

Yamamoto R, Nishikori M, Tashima M, Sakai T, Ichinohe T, Takaori-Kondo A, Ohmori K and Uchiyama T: B7-H1 expression is regulated by MEK/ERK signaling pathway in anaplastic large cell lymphoma and Hodgkin lymphoma. Cancer Sci. 100:2093–2100. 2009.PubMed/NCBI View Article : Google Scholar

31 

Jiang X, Zhou J, Giobbie-Hurder A, Wargo J and Hodi FS: The activation of MAPK in melanoma cells resistant to BRAF inhibition promotes PD-L1 expression that is reversible by MEK and PI3K inhibition. Clin Cancer Res. 19:598–609. 2013.PubMed/NCBI View Article : Google Scholar

32 

Atefi M, Avramis E, Lassen A, Wong DJ, Robert L, Foulad D, Cerniglia M, Titz B, Chodon T, Graeber TG, et al: Effects of MAPK and PI3K pathways on PD-L1 expression in melanoma. Clin Cancer Res. 20:3446–3457. 2014.PubMed/NCBI View Article : Google Scholar

33 

Mestas J and Hughes CC: Of mice and not men: Differences between mouse and human immunology. J Immunol. 172:2731–2738. 2004.PubMed/NCBI View Article : Google Scholar

34 

Davis MM: A prescription for human immunology. Immunity. 29:835–838. 2008.PubMed/NCBI View Article : Google Scholar

35 

Hayday AC and Peakman M: The habitual, diverse and surmountable obstacles to human immunology research. Nat Immunol. 9:575–580. 2008.PubMed/NCBI View Article : Google Scholar

36 

Naidoo J, Page DB, Li BT, Connell LC, Schindler K, Lacouture ME, Postow MA and Wolchok JD: Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Ann Oncol. 26:2375–2391. 2015.PubMed/NCBI View Article : Google Scholar

37 

Champiat S, Lambotte O, Barreau E, Belkhir R, Berdelou A, Carbonnel F, Cauquil C, Chanson P, Collins M, Durrbach A, et al: Management of immune checkpoint blockade dysimmune toxicities: A collaborative position paper. Ann Oncol. 27:559–574. 2016.PubMed/NCBI View Article : Google Scholar

38 

Shay T, Jojic V, Zuk O, Rothamel K, Puyraimond-Zemmour D, Feng T, Wakamatsu E, Benoist C, Koller D and Regev A: ImmGen Consortium: Conservation and divergence in the transcriptional programs of the human and mouse immune systems. Proc Natl Acad Sci USA. 110:2946–2951. 2013.PubMed/NCBI View Article : Google Scholar

39 

Diehl AG and Boyle AP: Conserved and species-specific transcription factor co-binding patterns drive divergent gene regulation in human and mouse. Nucleic Acids Res. 46:1878–1894. 2018.PubMed/NCBI View Article : Google Scholar

40 

Vierstra J, Rynes E, Sandstrom R, Zhang M, Canfield T, Hansen RS, Stehling-Sun S, Sabo PJ, Byron R, Humbert R, et al: Mouse regulatory DNA landscapes reveal global principles of cis-regulatory evolution. Science. 346:1007–1012. 2014.PubMed/NCBI View Article : Google Scholar

41 

Odom DT, Dowell RD, Jacobsen ES, Gordon W, Danford TW, MacIsaac KD, Rolfe PA, Conboy CM, Gifford DK and Fraenkel E: Tissue-specific transcriptional regulation has diverged significantly between human and mouse. Nat Genet. 39:730–732. 2007.PubMed/NCBI View Article : Google Scholar

42 

Harvey KF, Zhang X and Thomas DM: The Hippo pathway and human cancer. Nat Rev Cancer. 13:246–257. 2013.PubMed/NCBI View Article : Google Scholar

43 

Chen Q, Zhang N, Gray RS, Li H, Ewald AJ, Zahnow CA and Pan D: A temporal requirement for Hippo signaling in mammary gland differentiation, growth, and tumorigenesis. Genes Dev. 28:432–437. 2014.PubMed/NCBI View Article : Google Scholar

44 

Rech AJ and Vonderheide RH: Dynamic interplay of oncogenes and T cells induces PD-L1 in the tumor microenvironment. Cancer Discov. 3:1330–1332. 2013.PubMed/NCBI View Article : Google Scholar

45 

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. 13:84–88. 2007.PubMed/NCBI View Article : Google Scholar

46 

Casey SC, Tong L, Li Y, Do R, Walz S, Fitzgerald KN, Gouw AM, Baylot V, Gütgemann I, Eilers M and Felsher DW: MYC regulates the antitumor immune response through CD47 and PD-L1. Science. 352:227–231. 2016.PubMed/NCBI View Article : Google Scholar

47 

Gao Q, Wang XY, Qiu SJ, Yamato I, Sho M, Nakajima Y, Zhou J, Li BZ, Shi YH, Xiao YS, et al: Overexpression of PD-L1 significantly associates with tumor aggressiveness and postoperative recurrence in human hepatocellular carcinoma. Clin Cancer Res. 15:971–979. 2009.PubMed/NCBI View Article : Google Scholar

48 

Zhang P, Ma Y, Lv C, Huang M, Li M, Dong B, Liu X, An G, Zhang W, Zhang J, et al: Upregulation of programmed cell death ligand 1 promotes resistance response in non-small-cell lung cancer patients treated with neo-adjuvant chemotherapy. Cancer Sci. 107:1563–1571. 2016.PubMed/NCBI View Article : Google Scholar

49 

Gupta HB, Deng J, Clark CA, Drerup JM, Wu B, Sareddy G, Hurez V, Vadlamudi R, Li R and Curiel TJ: Programmed cell death ligand 1 (PD-L1) regulates tumor initiating cell (TIC) generation by controlling the stemness gene Oct4 through mTORC1. J Immunol. 200 (1 Supplement)(167)2018.

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Copy and paste a formatted citation
Spandidos Publications style
Zhang J, Yamada O, Kida S, Murase S, Hattori T, Oshima Y and Kikuchi H: Downregulation of PD‑L1 via amide analogues of brefelamide: Alternatives to antibody‑based cancer immunotherapy. Exp Ther Med 19: 3150-3158, 2020.
APA
Zhang, J., Yamada, O., Kida, S., Murase, S., Hattori, T., Oshima, Y., & Kikuchi, H. (2020). Downregulation of PD‑L1 via amide analogues of brefelamide: Alternatives to antibody‑based cancer immunotherapy. Experimental and Therapeutic Medicine, 19, 3150-3158. https://doi.org/10.3892/etm.2020.8553
MLA
Zhang, J., Yamada, O., Kida, S., Murase, S., Hattori, T., Oshima, Y., Kikuchi, H."Downregulation of PD‑L1 via amide analogues of brefelamide: Alternatives to antibody‑based cancer immunotherapy". Experimental and Therapeutic Medicine 19.4 (2020): 3150-3158.
Chicago
Zhang, J., Yamada, O., Kida, S., Murase, S., Hattori, T., Oshima, Y., Kikuchi, H."Downregulation of PD‑L1 via amide analogues of brefelamide: Alternatives to antibody‑based cancer immunotherapy". Experimental and Therapeutic Medicine 19, no. 4 (2020): 3150-3158. https://doi.org/10.3892/etm.2020.8553
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang J, Yamada O, Kida S, Murase S, Hattori T, Oshima Y and Kikuchi H: Downregulation of PD‑L1 via amide analogues of brefelamide: Alternatives to antibody‑based cancer immunotherapy. Exp Ther Med 19: 3150-3158, 2020.
APA
Zhang, J., Yamada, O., Kida, S., Murase, S., Hattori, T., Oshima, Y., & Kikuchi, H. (2020). Downregulation of PD‑L1 via amide analogues of brefelamide: Alternatives to antibody‑based cancer immunotherapy. Experimental and Therapeutic Medicine, 19, 3150-3158. https://doi.org/10.3892/etm.2020.8553
MLA
Zhang, J., Yamada, O., Kida, S., Murase, S., Hattori, T., Oshima, Y., Kikuchi, H."Downregulation of PD‑L1 via amide analogues of brefelamide: Alternatives to antibody‑based cancer immunotherapy". Experimental and Therapeutic Medicine 19.4 (2020): 3150-3158.
Chicago
Zhang, J., Yamada, O., Kida, S., Murase, S., Hattori, T., Oshima, Y., Kikuchi, H."Downregulation of PD‑L1 via amide analogues of brefelamide: Alternatives to antibody‑based cancer immunotherapy". Experimental and Therapeutic Medicine 19, no. 4 (2020): 3150-3158. https://doi.org/10.3892/etm.2020.8553
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