Inter J Stomatol ›› 2018, Vol. 45 ›› Issue (5): 560-565.doi: 10.7518/gjkq.2018.05.011

• Reviews • Previous Articles     Next Articles

Regulation of programmed death receptor-1 and its ligand signalling pathway and its progress in the treatment of head and neck squamous cell carcinoma

Lu Mao1,2,Houyu Ju1,Guoxin Ren1()   

  1. 1. Dept. of Oral and Maxillofacial Head and Neck Tumor, The Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, Shanghai 200011, China
    2. Weifang Medical University, Weifang 261053, China
  • Received:2017-12-31 Revised:2018-05-14 Online:2018-09-01 Published:2018-09-20
  • Contact: Guoxin Ren


Tumours are closely related to the immune system, and they can escape immune surveillance by stimulating immune inhibitory receptors, which can be blocked by the inhibitory receptors on the T cell. A potential strategy for anti-tumour immune therapy can be developed based on the abovementioned fact. Programmed death receptor-1 (PD-1)/programmed death-ligand 1 (PD-L1) is a newly identified negative co-stimulatory pathway that promotes immune escape. This review discusses the biological characteristics and functions of PD-1/PD-L1, as well as the application of PD-1/PD-L1 antibody in tumour therapy.

Key words: head and neck squamous carcinoma, programmed death receptor, programmed death ligand, immune checkpoint, immune escape

CLC Number: 

  • R730.3

[1] Li Y, Li F, Jiang F , et al. A mini-review for cancer immunotherapy: molecular understanding of PD-1/PD-L1 pathway & translational blockade of immune checkpoints[J]. Int J Mol Sci, 2016,17(7):1151.
doi: 10.3390/ijms17071151
[2] Hawkes EA, Grigg A, Chong G , Programmed cell death-1 inhibition in lymphoma[J]. Lancet Oncol, 2015,16(5):e234-e245.
doi: 10.1016/S1470-2045(15)70103-8 pmid: 25943068
[3] Luke JJ, Ott PA , PD-1 pathway inhibitors: the next generation of immunotherapy for advanced melanoma[J]. Oncotarget, 2015,6(6):3479-3492.
doi: 10.18632/oncotarget.2980 pmid: 4414130
[4] Dai S, Jia R, Zhang X , et al. The PD-1/PD-Ls pathway and autoimmune diseases[J]. Cell Immunol, 2014,290(1):72-79.
doi: 10.1016/j.cellimm.2014.05.006 pmid: 24908630
[5] Mamalis A, Garcha M, Jagdeo J , Targeting the PD-1 pathway: a promising future for the treatment of me- lanoma[J]. Arch Dermatol Res, 2014,306(6):511-519.
doi: 10.1007/s00403-014-1457-7 pmid: 4110159
[6] Calles A, Liao X, Sholl LM , et al. Expression of PD- 1 and its ligands, PD-L1 and PD-L2, in smokers and never smokers with KRAS-mutant lung cancer[J]. J Thorac Oncol, 2015,10(12):1726-1735.
doi: 10.1097/JTO.0000000000000687
[7] Dong H, Strome SE, Salomao DR , et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a po-tential mechanism of immune evasion[J]. Nat Med, 2002,8(8):793-800.
doi: 10.1038/nm730
[8] Suzuki S, Ishida T, Yoshikawa K , et al. Current status of immunotherapy[J]. Jpn J Clin Oncol, 2016,46(3):191-203
doi: 10.1093/jjco/hyv201
[9] Chen Y, Wang Q, Shi B , et al. Development of a sand-wich ELISA for evaluating soluble PD-L1 (CD274) in human sera of different ages as well as supernatants of PD-L1 + cell lines [J]. Cytokine, 2011,56(2):231-238.
doi: 10.1016/j.cyto.2011.06.004
[10] Rossille D, Gressier M, Damotte D , et al. High level of soluble programmed cell death ligand 1 in blood impacts overall survival in aggressive diffuse large B-cell lymphoma: results from a French multicenter clinical trial[J]. Leukemia, 2014,28(12):2367-2375.
doi: 10.1038/leu.2014.137
[11] Hawkes EA, Grigg A, Chong G , Programmed cell death-1 inhibition in lymphoma[J]. Lancet Oncol, 2015,16(5):e234-e245.
doi: 10.1016/S1470-2045(15)70103-8 pmid: 25943068
[12] Francisco LM, Salinas VH, Brown KE , et al. PD-L1 regulates the development, maintenance, and func-tion of induced regulatory T cells[J]. J Exp Med, 2009,206(13):3015-3029.
doi: 10.1016/j.clim.2009.03.115 pmid: 2806460844606795052401422
[13] Haxhinasto S, Mathis D, Benoist C , The AKT-mTOR axis regulates de novo differentiation of CD4 +Foxp3+ cells [J]. J Exp Med, 2008,205(3):565-574.
doi: 10.1084/jem.20071477
[14] Austin JW, Lu P, Majumder P , et al. STAT3, STAT4, NFATc1, and CTCF regulate PD-1 through multiple novel regulatory regions in murine T cells[J]. J Im-munol, 2014,192(10):4876-4886.
[15] Oestreich KJ, Yoon H, Ahmed R , et al. NFATc1 regulates PD-1 expression upon T cell activation[J]. J Immunol, 2008,181(7):4832-4839.
doi: 10.4049/jimmunol.181.7.4832 pmid: 18802087
[16] Staron MM, Gray SM, Marshall HD , et al. The trans-cription factor FoxO1 sustains expression of the inhibitory receptor PD-1 and survival of antiviral CD8 + T cells during chronic infection [J]. Immunity, 2014,41(5):802-814.
doi: 10.1016/j.immuni.2014.10.013
[17] Lee SJ, Jang BC, Lee SW , et al. Interferon regulatory factor-1 is prerequisite to the constitutive expression and IFN-γ-induced upregulation of B7-H1 (CD274)[J]. FEBS Lett, 2006,580(3):755-762.
doi: 10.1016/j.febslet.2005.12.093
[18] Parsa AT, Waldron JS, Panner A , et al. Loss of tumor suppressor PTEN function increases B7-H1 expre-ssion and immunoresistance in glioma[J]. Nat Med, 2007,13(1):84-88.
doi: 10.1038/nm1517
[19] Akbay EA, Koyama S, Carretero J , et al. Activation of the PD-1 pathway contributes to immune escape in EGFR-driven lung tumors[J]. Cancer Discov, 2013,3(12):1355-1363.
doi: 10.1158/2159-8290.CD-13-0310
[20] Kakavand H, Wilmott JS, Menzies AM , et al. PD-L1 expression and tumor-infiltrating lymphocytes define different subsets of MAPK inhibitor-treated melanoma patients[J]. Clin Cancer Res, 2015,21(14):3140-3148.
doi: 10.1158/1078-0432.CCR-14-2023
[21] 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]. J Exp Med, 2014,211(5):781-790.
doi: 10.1084/jem.20131916
[22] Chen L, Gibbons DL, Goswami S , et al. Metastasis is regulated via microRNA-200/ZEB1 axis control of tumour cell PD-L1 expression and intratumoral immunosuppression[J]. Nat Commun, 2014,5:5241.
doi: 10.1038/ncomms6241
[23] Gong AY, Zhou R, Hu G , et al. MicroRNA-513 regulates B7-H1 translation and is involved in IFN-γ-induced B7-H1 expression in cholangiocytes[J]. J Immunol, 2009,182(3):1325-1333.
doi: 10.4049/jimmunol.182.3.1325
[24] Hsu MC, Hsiao JR, Chang KC , et al. Increase of programmed death-1-expressing intratumoral CD8 T cells predicts a poor prognosis for nasopharyngeal carcinoma[J]. Mod Pathol, 2010,23(10):1393-1403.
doi: 10.1038/modpathol.2010.130
[25] Badoual C, Hans S, Merillon N , et al. PD-1-expressing tumor-infiltrating T cells are a favorable prognostic biomarker in HPV-associated head and neck cancer[J]. Cancer Res, 2013,73(1):128-138.
[26] Ukpo OC, Thorstad WL, Lewis JS Jr , B7-H1 ex-pression model for immune evasion in human pa-pillomavirus-related oropharyngeal squamous cell carcinoma[J]. Head Neck Pathol, 2013,7(2):113-121.
doi: 10.1007/s12105-012-0406-z
[27] Cho YA, Yoon HJ, Lee JI , et al. Relationship be-tween the expressions of PD-L1 and tumor-infiltra-ting lymphocytes in oral squamous cell carcinoma[J]. Oral Oncol, 2011,47(12):1148-1153.
doi: 10.1016/j.oraloncology.2011.08.007
[28] 张峰, 刘争, 崔永华 , 等. 鼻咽癌组织中程序性死亡配体-1的表达及其临床意义[J]. 临床耳鼻咽喉头颈外科杂志, 2008,22(9):408-410.
doi: 10.3969/j.issn.1001-1781.2008.09.007
Zhang F, Liu Z, Cui YH , et al. The clinical signifi-cance of the expression of costimulatory molecule PD-L1 in nasopharyngeal carcinoma[J]. J Clin Otor-hinolaryngol Head Neck Surg, 2008,22(9):408-410.
doi: 10.3969/j.issn.1001-1781.2008.09.007
[29] Brahmer JR, Tykodi SS, Chow LQ , et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer[J]. N Engl J Med, 2012,366(26):2455-2465.
doi: 10.1016/j.juro.2012.08.169 pmid: 22658128
[30] Gibbons DL, Chow LQ, Kim DW , et al. Efficacy, sa-fety and tolerability of MEDI4736 (durvalumab [D]), a human IgG1 anti-programmed cell death-ligand-1 (PD-L1) antibody, combined with gefitinib (G): a phase Ⅰ expansion in TKI-naive patients (pts) with EGFR mutant NSCLC[J]. J Thorac Oncol, 2016,11(4 Suppl):S79-S91.
[31] Segal NH, Ou SH, Balmanoukian AS , et al. Updated safety and efficacy of durvalumab (MEDI4736), an anti-PD-L 1 antibody, in patients from a squamous cell carcinoma of the head and neck (SCCHN) ex-pansion cohort[J]. Ann Oncol, 2016,27(Suppl 6):9490.
[32] Ang YL, Tan HL, Soo RA , Best practice in the treat-ment of advanced squamous cell lung cancer[J]. Ther Adv Respir Dis, 2015,9(5):224-235.
doi: 10.1177/1753465815581147 pmid: 25902866
[33] Seiwert TY, Burtness B, Weiss J , et al. A phase iB study of MK-3475 in patients with human papillo-mavirus (HPV)-associated and non-HPV associated head and neck (H/N) cancer[J]. J Clin Oncol, 2014,32(5):386s.
[34] Ferris RL, Blumenschein G Jr, Fayette J , et al. Nivo-lumab for recurrent squamous-cell carcinoma of the head and neck[J]. N Engl J Med, 2016,375(19):1856-1867.
doi: 10.1056/NEJMoa1602252 pmid: 27718784
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[7] . [J]. Foreign Med Sci: Stomatol, 2005, 32(06): 458 -460 .
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