国际口腔医学杂志 ›› 2018, Vol. 45 ›› Issue (5): 560-565.doi: 10.7518/gjkq.2018.05.011

• 综述 • 上一篇    下一篇

程序性细胞死亡受体-1与其配体信号通路的调控及其在头颈鳞状细胞癌治疗中的研究进展

毛璐1,2,鞠侯雨1,任国欣1()   

  1. 1. 上海交通大学医学院附属第九人民医院口腔颌面头颈肿瘤科 上海市口腔医学重点实验室/上海市口腔医学研究所 国家口腔疾病临床研究中心 上海 200011
    2. 潍坊医学院 潍坊 261053
  • 收稿日期:2017-12-31 修回日期:2018-05-14 出版日期:2018-09-01 发布日期:2018-09-20
  • 通讯作者: 任国欣
  • 作者简介:毛璐,硕士,Email:maolultj@163.com

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

摘要:

肿瘤通过刺激免疫系统的抑制受体改变原有免疫反应,进行免疫逃逸。通过阻断T细胞抑制受体,阻断肿瘤的发生,为抗肿瘤免疫提供了潜在的治疗策略。已证实程序性细胞死亡受体-1(PD-1)/程序性细胞死亡配体-1(PD-L1)能够通过抑制T细胞的活化、增殖及细胞因子的产生来负调控免疫应答,促进肿瘤逃逸。本文综述了PD-1/PD-L1信号通路的生物学特点及功能,并回顾了抗PD-1/PD-L1治疗头颈部肿瘤的研究进展。

关键词: 头颈部鳞状细胞癌, 程序性细胞死亡受体, 程序性细胞死亡配体, 免疫检查点, 免疫逃逸

Abstract:

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

中图分类号: 

  • 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
[1] 刘世一, 陈中, 张素欣. 程序性死亡受体/配体免疫治疗策略在人乳头瘤病毒阳性头颈部鳞状细胞癌中的研究进展[J]. 国际口腔医学杂志, 2024, 51(1): 21-27.
[2] 李奕君, 徐子昂, 李一. 前哨淋巴结在头颈部鳞状细胞癌检测的应用进展[J]. 国际口腔医学杂志, 2023, 50(5): 521-527.
[3] 徐智博,孟秀萍. 粪肠球菌逃逸宿主免疫防御机制的研究进展[J]. 国际口腔医学杂志, 2023, 50(5): 613-617.
[4] 李洪芳,陈中,张素欣. 免疫检查点抑制剂联合放射治疗在头颈部鳞状细胞癌治疗中的研究进展[J]. 国际口腔医学杂志, 2022, 49(5): 614-620.
[5] 郝福,孙睿. 头颈部鳞状细胞癌第二原发癌的研究进展[J]. 国际口腔医学杂志, 2019, 46(5): 585-592.
[6] 李格格, 潘佳慧, 唐秋玲, 刘歆婵, 侯玉帛, 于维先. 牙龈素促进牙龈卟啉单胞菌免疫逃逸的机制[J]. 国际口腔医学杂志, 2017, 44(5): 519-522.
[7] 张静1综述 周刚1,2审校. 程序性细胞死亡-1/程序性细胞死亡配体-1 信号途径及其对口腔慢性疾病的作用[J]. 国际口腔医学杂志, 2012, 39(1): 69-72.
[8] 李金,廖贵清,. TEXs在肿瘤免疫中的研究进展[J]. 国际口腔医学杂志, 2006, 33(06): 451-453.
[9] 黄静,陈新明. 单核苷酸多态与头颈部鳞状细胞癌发生风险的研究进展[J]. 国际口腔医学杂志, 2005, 32(04): 269-271.
[10] 王志国,褚存超,郭伟. 比较基因组杂交技术在头颈部鳞癌诊断中的研究进展[J]. 国际口腔医学杂志, 2004, 31(05): 365-367.
[11] 魏昕 周学东 陈谦明. 染色体异常与口腔和头颈部鳞状细胞癌[J]. 国际口腔医学杂志, 2003, 30(03): 167-169.
[12] 陈伟辉. 头颈部鳞状细胞癌及口腔癌的染色体畸变[J]. 国际口腔医学杂志, 1999, 26(02): -.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
[1] 张新春. 桩冠修复与无髓牙的保护[J]. 国际口腔医学杂志, 1999, 26(06): .
[2] 王昆润. 长期单侧鼻呼吸对头颅发育有不利影响[J]. 国际口腔医学杂志, 1999, 26(05): .
[3] 彭国光. 颈淋巴清扫术中颈交感神经干的解剖变异[J]. 国际口腔医学杂志, 1999, 26(05): .
[4] 杨凯. 淋巴化疗的药物运载系统及其应用现状[J]. 国际口腔医学杂志, 1999, 26(05): .
[5] 康非吾. 种植义齿下部结构生物力学研究进展[J]. 国际口腔医学杂志, 1999, 26(05): .
[6] 柴枫. 可摘局部义齿用Co-Cr合金的激光焊接[J]. 国际口腔医学杂志, 1999, 26(04): .
[7] 孟姝,吴亚菲,杨禾. 伴放线放线杆菌产生的细胞致死膨胀毒素及其与牙周病的关系[J]. 国际口腔医学杂志, 2005, 32(06): 458 -460 .
[8] 费晓露,丁一,徐屹. 牙周可疑致病菌对口腔黏膜上皮的粘附和侵入[J]. 国际口腔医学杂志, 2005, 32(06): 452 -454 .
[9] 赵兴福,黄晓晶. 变形链球菌蛋白组学研究进展[J]. 国际口腔医学杂志, 2008, 35(S1): .
[10] 庞莉苹,姚江武. 抛光和上釉对陶瓷表面粗糙度、挠曲强度及磨损性能的影响[J]. 国际口腔医学杂志, 2008, 35(S1): .