山东大学耳鼻喉眼学报 ›› 2023, Vol. 37 ›› Issue (5): 135-141.doi: 10.6040/j.issn.1673-3770.0.2022.214

• 综述 • 上一篇    下一篇

鼻咽癌中抗PD-L1/PD-1治疗及非编码RNA调控研究进展

涂巧铃1,李玉凤2,彭军3   

  1. 1.华北理工大学 研究生学院, 河北 唐山 063200;
    2.唐山市人民医院 中心实验室, 河北 唐山 063000;
    3.唐山市人民医院 耳鼻咽喉头颈外科, 河北 唐山 063000
  • 发布日期:2023-10-13
  • 通讯作者: 彭军. E-mail:pengjun1110@126.com
  • 基金资助:
    河北省分子肿瘤学重点实验室(SZX2020043)

Advances in anti-PD-L1/PD-1 therapy and non-coding RNA regulation in nasopharyngeal carcinoma

TU Qiaoling1, LI Yufeng2, PENG Jun3   

  1. 1. Graduate School, North China University of Science and Technology, Tangshan 063200, Hebei, China2. Central Laboratory, Tangshan People's Hospital, Tangshan 063000, Hebei, China3. Department of Otorhinolaryngology & Head and Neck Surgery, Tangshan People's Hospital, Tangshan 063000, Hebei, China
  • Published:2023-10-13

摘要: 鼻咽癌(nasopharyngeal carcinoma, NPC)是一种来源于鼻咽上皮组织的头颈部恶性肿瘤,临床难点为晚期或复发患者的治疗,目前研究表明免疫治疗对患者有效。程序性死亡配体1(programmed death ligand 1, PD-L1)在NPC组织中表达增加,与T细胞表面的程序性死亡受体1(programmed death receptor 1, PD-1)结合能抑制T细胞的激活,导致NPC免疫逃逸。非编码RNA在调节NPC发生发展中发挥重要作用,寻找能够调节PD-L1/PD-1轴的上游非编码RNA可以为NPC的免疫治疗提供新思路。论文对PD-L1/PD-1轴在NPC免疫治疗中的作用及相关非编码RNA调控的研究进展进行综述。

关键词: 鼻咽癌, 程序性死亡配体1/程序性死亡受体1, 非编码RNA, 免疫治疗, 分子机制

Abstract: Nasopharyngeal carcinoma(NPC)is a malignant head and neck tumor type derived from nasopharyngeal epithelium. Successful treatment of patients with advanced or recurrent NPC remains difficult. Recent studies have shown that immunotherapy is effective for these patients. Programmed death ligand 1(PD-L1)is highly expressed in NPC. PD-L1 binding to programmed death receptor 1(PD-1)on the surface of T cells can inhibit T cell activation, leading to immune escape by NPC. Non-coding RNA plays important roles in regulating the occurrence and development of NPC. Searching for upstream ncRNAs that can regulate the PD-L1/PD-1 axis can provide new ideas for immunotherapy of NPC. This article reviews the role of the PD-L1/PD-1 axis in NPC immunotherapy and summarizes progress of research related to ncRNA regulation.

Key words: Nasopharyngeal carcinoma, Programmed death ligand 1/ programmed death receptor 1, Non-coding RNA, Immunotherapy, Molecular mechanism

中图分类号: 

  • R739.6
[1] 方三高, 魏建国, 周晓军. 解读WHO(2017)头颈部肿瘤分类(鼻腔、鼻窦、颅底)[J]. 诊断病理学杂志, 2018, 25(4): 241-245. doi:10.3969/j.issn.1007-8096.2018.04.001
[2] Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249. doi:10.3322/caac.21660
[3] Chang ET, Ye W, Zeng YX, et al. The evolving epidemiology of nasopharyngeal carcinoma[J]. Cancer Epidemiol Biomarkers Prev, 2021, 30(6): 1035-1047. doi:10.1158/1055-9965.EPI-20-1702
[4] Kuang-Rong Wei, Rong-Shou Zheng, Si-Wei Zhang, 等. 2013年中国鼻咽癌发病和死亡分析[J]. 癌症, 2018, 37(4): 170-178
[5] Chen YP, Chan ATC, Le QT, et al. Nasopharyngeal carcinoma[J]. Lancet, 2019, 394(10192): 64-80. doi:10.1016/S0140-6736(19)30956-0
[6] Perri F, Della Vittoria Scarpati G, Caponigro F, et al. Management of recurrent nasopharyngeal carcinoma: current perspectives[J]. Onco Targets Ther, 2019, 12: 1583-1591. doi:10.2147/OTT.S188148
[7] Lee AWM, Ng WT, Chan JYW, et al. Management of locally recurrent nasopharyngeal carcinoma[J]. Cancer Treat Rev, 2019, 79: 101890. doi:10.1016/j.ctrv.2019.101890
[8] Zhang Y, Chen L, Hu GQ, et al. Gemcitabine and cisplatin induction chemotherapy in nasopharyngeal carcinoma[J]. N Engl J Med, 2019, 381(12): 1124-1135. doi:10.1056/NEJMoa1905287
[9] Lv JW, Li JY, Luo LN, et al. Comparative safety and efficacy of anti-PD-1 monotherapy, chemotherapy alone, and their combination therapy in advanced nasopharyngeal carcinoma: findings from recent advances in landmark trials[J]. J Immunother Cancer, 2019, 7(1): 159. doi:10.1186/s40425-019-0636-7
[10] Chow JC, Ngan RK, Cheung KM, et al. Immunotherapeutic approaches in nasopharyngeal carcinoma[J]. Expert Opin Biol Ther, 2019, 19(11): 1165-1172. doi:10.1080/14712598.2019.1650910
[11] Guo Z, Wang YH, Xu H, et al. LncRNA linc00312 suppresses radiotherapy resistance by targeting DNA-PKcs and impairing DNA damage repair in nasopharyngeal carcinoma[J]. Cell Death Dis, 2021, 12(1): 69. doi:10.1038/s41419-020-03302-2
[12] Hong X, Liu N, Liang Y, et al. Circular RNA CRIM1 functions as a ceRNA to promote nasopharyngeal carcinoma metastasis and docetaxel chemoresistance through upregulating FOXQ1[J]. Mol Cancer, 2020, 19(1): 33. doi:10.1186/s12943-020-01149-x
[13] Blanchard P, Lee A, Marguet S, et al. Chemotherapy and radiotherapy in nasopharyngeal carcinoma: an update of the MAC-NPC meta-analysis[J]. Lancet Oncol, 2015, 16(6): 645-655. doi:10.1016/S1470-2045(15)70126-9
[14] Yang P, Zhou T, Chen X, et al. Efficacy, safety, and biomarker analysis of camrelizumab in previously treated recurrent or metastatic nasopharyngeal carcinoma(CAPTAIN study)[J]. J Immunother Cancer, 2021, 9(12): e003790. doi:10.1136/jitc-2021-003790
[15] Larbcharoensub N, Mahaprom K, Jiarpinitnun C, et al. Characterization of PD-L1 and PD-1 expression and CD8+ tumor-infiltrating lymphocyte in Epstein-Barr virus-associated nasopharyngeal carcinoma[J]. Am J Clin Oncol, 2018, 41(12): 1204-1210. doi:10.1097/COC.0000000000000449
[16] Lau KM, Cheng SH, Lo KW, et al. Increase in circulating Foxp3+CD4+CD25(high)regulatory T cells in nasopharyngeal carcinoma patients[J]. Br J Cancer, 2007, 96(4): 617-622. doi:10.1038/sj.bjc.6603580
[17] Ding L, Lu S, Li Y. Regulation of PD-1/PD-L1 pathway in cancer by noncoding RNAs[J]. Pathol Oncol Res, 2020, 26(2): 651-663. doi:10.1007/s12253-019-00735-9
[18] Keir ME, Butte MJ, Freeman GJ, et al. PD-1 and its ligands in tolerance and immunity[J]. Annu Rev Immunol, 2008, 26: 677-704. doi:10.1146/annurev.immunol.26.021607.090331
[19] Dong HD, Strome SE, Salomao DR, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion[J]. Nat Med, 2002, 8(8): 793-800. doi:10.1038/nm730
[20] Sun C, Mezzadra R, Schumacher TN. Regulation and function of the PD-L1 checkpoint[J]. Immunity, 2018, 48(3): 434-452. doi:10.1016/j.immuni.2018.03.014
[21] Zhao R, Song Y, Wang Y, et al. PD-1/PD-L1 blockade rescue exhausted CD8+ T cells in gastrointestinal stromal tumours via the PI3K/Akt/mTOR signalling pathway[J]. Cell Prolif, 2019, 52(3): e12571. doi:10.1111/cpr.12571
[22] Piao W, Li L, Saxena V, et al. PD-L1 signaling selectively regulates T cell lymphatic transendothelial migration[J]. Nat Commun, 2022, 13(1): 2176. doi:10.1038/s41467-022-29930-0
[23] Wang YQ, Zhang Y, Jiang W, et al. Development and validation of an immune checkpoint-based signature to predict prognosis in nasopharyngeal carcinoma using computational pathology analysis[J]. J Immunother Cancer, 2019, 7(1): 298. doi:10.1186/s40425-019-0752-4
[24] Fang W, Yang Y, Ma Y, et al. Camrelizumab(SHR-1210)alone or in combination with gemcitabine plus cisplatin for nasopharyngeal carcinoma: results from two single-arm, phase 1 trials[J]. Lancet Oncol, 2018, 19(10): 1338-1350. doi:10.1016/S1470-2045(18)30495-9
[25] Ma BBY, Lim WT, Goh BC, et al. Antitumor activity of nivolumab in recurrent and metastatic nasopharyngeal carcinoma: an international, multicenter study of the mayo clinic phase 2 consortium(NCI-9742)[J]. J Clin Oncol, 2018, 36(14): 1412-1418. doi:10.1200/JCO.2017.77.0388
[26] Even C, Wang HM, Li SH, et al. Phase II, randomized study of spartalizumab(PDR001), an anti-PD-1 antibody, versus chemotherapy in patients with recurrent/metastatic nasopharyngeal cancer[J]. Clin Cancer Res, 2021, 27(23): 6413-6423. doi:10.1158/1078-0432.CCR-21-0822
[27] Wang FH, Wei XL, Feng J, et al. Efficacy, safety, and correlative biomarkers of toripalimab in previously treated recurrent or metastatic nasopharyngeal carcinoma: a phase II clinical trial(POLARIS-02)[J]. J Clin Oncol, 2021, 39(7): 704-712. doi:10.1200/JCO.20.02712
[28] Makowska A, Meier S, Shen L, et al. Anti-PD-1 antibody increases NK cell cytotoxicity towards nasopharyngeal carcinoma cells in the context of chemotherapy-induced upregulation of PD-1 and PD-L1[J]. Cancer Immunol Immunother, 2021, 70(2): 323-336. doi:10.1007/s00262-020-02681-x
[29] Yuan Y, Adam A, Zhao C, et al. Recent advancements in the mechanisms underlying resistance to PD-1/PD-L1 blockade immunotherapy[J]. Cancers(Basel), 2021, 13(4): 663. doi:10.3390/cancers13040663
[30] Zhang P, Wu W, Chen Q, et al. Non-coding RNAs and their integrated networks[J]. J Integr Bioinform, 2019, 16(3): 20190027. doi:10.1515/jib-2019-0027
[31] Mohr AM, Mott JL. Overview of microRNA biology[J]. Semin Liver Dis, 2015, 35(1): 3-11. doi:10.1055/s-0034-1397344
[32] Wu RS, Qiu EH, Zhu JJ, et al. miR-101 promotes nasopharyngeal carcinoma cell apoptosis through inhibiting Ras/Raf/MEK/ERK signaling pathway[J]. Eur Rev Med Pharmacol Sci, 2020, 24(16): 8240. doi:10.26355/eurrev_202008_22580
[33] Liu YL, Yang WH, Chen BY, et al. miR-29b suppresses proliferation and induces apoptosis of hepatocellular carcinoma ascites H22 cells via regulating TGF-β1 and p53 signaling pathway[J]. Int J Mol Med, 2021, 48(2): 157. doi:10.3892/ijmm.2021.4990
[34] Kooshkaki O, Rezaei Z, Rahmati M, et al. miR-144: a new possible therapeutic target and diagnostic/prognostic tool in cancers[J]. Int J Mol Sci, 2020, 21(7): E2578. doi:10.3390/ijms21072578
[35] Huang W, Song W, Jiang Y, et al. C-Myc-induced circ-NOTCH1 promotes aggressive phenotypes of nasopharyngeal carcinoma cells by regulating the miR-34c-5p/c-Myc axis[J]. Cell Biol Int, 2021, 45(7): 1436-1447. doi:10.1002/cbin.11582
[36] Chen M, Chen C, Luo H, et al. MicroRNA-296-5p inhibits cell metastasis and invasion in nasopharyngeal carcinoma by reversing transforming growth factor-β-induced epithelial-mesenchymal transition[J]. Cell Mol Biol Lett, 2020, 25(1): 49. doi:10.1186/s11658-020-00240-x
[37] Han JB, Huang ML, Li F, et al. MiR-214 mediates cell proliferation and apoptosis of nasopharyngeal carcinoma through targeting both WWOX and PTEN[J]. Cancer Biother Radiopharm, 2020, 35(8): 615-625. doi:10.1089/cbr.2019.2978
[38] Ashrafizadeh M, Zarrabi A, Hushmandi K, et al. PD-1/PD-L1 axis regulation in cancer therapy: the role of long non-coding RNAs and microRNAs[J]. Life Sci, 2020, 256: 117899. doi:10.1016/j.lfs.2020.117899
[39] Zhang Y, Zhu R, Wang J, et al. Upregulation of lncRNA H19 promotes nasopharyngeal carcinoma proliferation and metastasis in let-7 dependent manner[J]. Artif Cells Nanomed Biotechnol, 2019, 47(1): 3854-3861. doi:10.1080/21691401.2019.1669618
[40] Zheng YJ, Zhao JY, Liang TS, et al. Long noncoding RNA SMAD5-AS1 acts as a microRNA-106a-5p sponge to promote epithelial mesenchymal transition in nasopharyngeal carcinoma[J]. FASEB J, 2019, 33(11): 12915-12928. doi:10.1096/fj.201900803R
[41] Zhang W, Guo Q, Liu G, et al. NKILA represses nasopharyngeal carcinoma carcinogenesis and metastasis by NF-κB pathway inhibition[J]. PLoS Genet, 2019, 15(8): e1008325. doi:10.1371/journal.pgen.1008325
[42] Mo Y, Wang Y, Zhang S, et al. Circular RNA circRNF13 inhibits proliferation and metastasis of nasopharyngeal carcinoma via SUMO2[J]. Mol Cancer, 2021, 20(1): 112. doi:10.1186/s12943-021-01409-4
[43] Fan C, Qu H, Xiong F, et al. CircARHGAP12 promotes nasopharyngeal carcinoma migration and invasion via ezrin-mediated cytoskeletal remodeling[J]. Cancer Lett, 2021, 496: 41-56. doi:10.1016/j.canlet.2020.09.006
[44] Yu H, Zhang C, Li W, et al. Nano-coated si-SNHG14 regulated PD-L1 expression and decreased epithelial-mesenchymal transition in nasopharyngeal carcinoma cells[J]. J Biomed Nanotechnol, 2021, 17(10): 1993-2002. doi:10.1166/jbn.2021.3162
[45] Tang Y, He Y, Shi L, et al. Co-expression of AFAP1-AS1 and PD-1 predicts poor prognosis in nasopharyngeal carcinoma[J]. Oncotarget, 2017, 8(24): 39001-39011. doi:10.18632/oncotarget.16545
[46] Wang S, You H, Yu S. Long non-coding RNA HOXA-AS2 promotes the expression levels of hypoxia-inducible factor-1α and programmed death-ligand 1, and regulates nasopharyngeal carcinoma progression via miR-519[J]. Oncol Lett, 2020, 20(5): 245. doi:10.3892/ol.2020.12107
[47] Ge J, Wang J, Xiong F, et al. Epstein-Barr virus-encoded circular RNA CircBART2.2 promotes immune escape of nasopharyngeal carcinoma by regulating PD-L1[J]. Cancer Res, 2021, 81(19): 5074-5088. doi:10.1158/0008-5472.CAN-20-4321
[48] Wang J, Ge J, Wang Y, et al. EBV miRNAs BART11 and BART17-3p promote immune escape through the enhancer-mediated transcription of PD-L1[J]. Nat Commun, 2022, 13(1): 866. doi:10.1038/s41467-022-28479-2
[49] Wu Q, Zhao Y, Sun Y, et al. miR-375 inhibits IFN-γ-induced programmed death 1 ligand 1 surface expression in head and neck squamous cell carcinoma cells by blocking JAK2/STAT1 signaling[J]. Oncol Rep, 2018, 39(3): 1461-1468. doi:10.3892/or.2018.6177
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