免疫检查点抑制剂治疗口腔鳞癌的研究进展

doi:10.11904/j.issn.1002-3070.2022.01.015

摘要/Abstract

摘要： 口腔鳞状细胞癌(Oral squamous cell carcinoma,OSCC)是口腔头颈部肿瘤的常见类型,显著的病理特征为免疫抑制和淋巴细胞的浸润。癌细胞常常通过激活不同的免疫检查点逃避免疫监视,从而躲过机体抗肿瘤免疫反应。目前的治疗方法都有一定的局限性,且毒副作用较大。因此,研究和开发新的治疗手段和给药途径尤为重要。免疫检查点抑制剂(Immune checkpoint inhibitors,ICIs)的引入带动了OSCC临床治疗模式的转变。在这篇综述中,我们讨论了抗细胞程序性死亡受体1(Programmed cell death protein 1,PD-1)治疗OSCC的优势,并综述了目前可用于预测疗效的生物标记物的相关进展。

关键词: 鳞癌, 免疫疗法, 生物标记物, 细胞程序性死亡受体

Abstract: Oral squamous cell carcinoma(OSCC)is a common type of oral head and neck tumors.The significant pathological features are immunosuppression and lymphocyte infiltration.Tumor cells often evade immune surveillance by activating different immune checkpoints,thereby avoiding the body's anti-tumor immune response.The current treatment methods have certain limitations,and the side effects are relatively large.Therefore,it is particularly important to research and develop new treatment methods and routes of administration.The introduction of immune checkpoint inhibitors(ICIs)has led to a shift in the clinical treatment model of OSCC.This article discusses the advantages of the anti-programmed cell death protein 1(PD-1)in the treatment of OSCC,and reviews the current developments in biomarkers that can be used to predict efficacy.

Key words: Squamous cell carcinoma, Immunotherapy, Biomarker, Programmed cell death receptor

中图分类号:

R739.81

王思然, 胡伟平. 免疫检查点抑制剂治疗口腔鳞癌的研究进展[J]. 实用肿瘤学杂志, 2022, 36(1): 79-83.

WANG Siran, HU Weiping. Research progress of immune checkpoint inhibitors in the treatment of oral squamous cell carcinoma[J]. Journal of Practical Oncology, 2022, 36(1): 79-83.

参考文献

1 de Vicente JC,Rodríguez-Santamarta T,Rodrigo JP,et al.PD-L1 expression in tumor cells is an independent unfavorable prognostic factor in oral squamous cell carcinoma[J].Cancer Epidemiol Biomarkers Prev,2019,28(3):546-554.
2 Shaw R,Beasley N.Aetiology and risk factors for head and neck cancer:United Kingdom national multidisciplinary guidelines[J].J Laryngol Otol,2016,130(2):9-12.
3 Kaidar-Person O,Gil Z,Billan S.Precision medicine in head and neck cancer[J].Drug Resist Updat,2018,40:13-16.
4 Goertzen C,Mahdi H,Laliberte C,et al.Oral inflammation promotes oral squamous cell carcinoma invasion[J].Oncotarget,2018,9(49):29047-29063.
5 Pai-Scherf L,Blumenthal GM,Li H,et al.FDA approval summary:pembrolizumab for treatment of metastatic non-small cell lung cancer:first-line therapy and beyond[J].Oncologist,2017,22(11):1392-1399.
6 Takahashi H,Sakakura K,Arisaka Y,et al.Clinical and biological significance of PD-L1 expression within the tumor microenvironment of oral squamous cell carcinoma[J].Anticancer Res,2019,39(6):3039-3046.
7 Ishida Y,Agata Y,Shibahara K,et al.Induced expression of PD-1,a novel member of the immunoglobulin gene superfamily,upon programmed cell death[J].EMBO J,1992,11(11):3887-3895.
8 Kim JW,Lee J,Hong SM,et al.Circulating CCR7^loPD-1^hi follicular helper T cells indicate disease activity and glandular inflammation in patients with primary Sjögren's Syndrome[J].Immune Netw,2019,19(4):e26.
9 Fonseca VR,Romão VC,Agua-Doce A,et al.The ratio of blood T follicular regulatory cells to T follicular helper cells marks ectopic lymphoid structure formation while activated follicular helper T cells indicate disease activity in primary Sjögren's Syndrome[J].Arthritis Rheumatol,2018,70(5):774-784.
10 Hirai M,Kitahara H,Kobayashi Y,et al.Regulation of PD-L1 expression in a high-grade invasive human oral squamous cell carcinoma microenvironment[J].Int J Oncol,2017,50(1):41-48.
11 Meehan K,Leslie C,Lucas M,et al.Characterization of the immune profile of oral tongue squamous cell carcinomas with advancing disease[J].Cancer Med,2020,9(13):4791-4807.
12 Ribas A.Tumor immunotherapy directed at PD-1[J].N Engl J Med,2012,366(26):2517-2519.
13 Sun C,Mezzadra R,Schumacher TN.Regulation and function of the PD-L1 checkpoint[J].Immunity,2018,48(3):434-452.
14 Sznol M,Chen L.Antagonist antibodies to PD-1 and B7-H1(PD-L1)in the treatment of advanced human cancer[J].Clin Cancer Res,2013,19(5):1021-1034.
15 Mann JE,Hoesli R,Michmerhuizen NL,et al.Surveilling the potential for precision medicine-driven PD-1/PD-L1-targeted therapy in HNSCC[J].J Cancer,2017,8(3):332-344.
16 Sullivan RJ,Flaherty KT.Pembrolizumab for treatment of patients with advanced or unresectable melanoma[J].Clin Cancer Res,2015,21(13):2892-2897.
17 Ferris RL,Blumenschein G Jr,Fayette J,et al.Nivolumab for recurrent squamous-cell carcinoma of the head and neck[J].N Engl J Med,2016,375(19):1856-1867.
18 Nivolumab doubles survival for patients with HNSCC[J].Cancer Discov,2016,6(7):3.
19 Rose S.Pembrolizumab has antitumor activity in advanced head and neck cancer[J].Cancer Discovery,2016,6(7):693.
20 Cohen EEW,Soulières D,Le Tourneau C,et al.Pembrolizumab versus methotrexate,docetaxel,or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma(KEYNOTE-040):a randomised,open-label,phase 3 study[J].Lancet,2019,393(10167):156-167.
21 Foy JP,Bertolus C,Michallet MC,et al.The immune microenvironment of HPV-negative oral squamous cell carcinoma from never-smokers and never-drinkers patients suggests higher clinical benefit of IDO1 and PD1/PD-L1 blockade[J].Ann Oncol,2017,28(8):1934-1941.
22 Cai Y,Wang F,Liu Q,et al.A novel humanized anti-PD-1 monoclonal antibody potentiates therapy in oral squamous cell carcinoma[J].Invest New Drugs,2019,37(5):799-809.
23 张连齐,李吉辰,朴松林,等.PD-L1与MTA1在口腔鳞癌中的表达与临床意义[J].实用肿瘤学杂志,2020,34(3):220-224.
24 Zandberg DP,Algazi AP,Jimeno A,et al.Durvalumab for recurrent or metastatic head and neck squamous cell carcinoma:results from a single-arm,phase II study in patients with ≥25% tumour cell PD-L1 expression who have progressed on platinum-based chemotherapy[J].Eur J Cancer,2019,107:142-152.
25 Zandberg D,Algazi A,Jimeno A,et al.1042Odurvalumab for recurrent/metastatic(r/m)head and neck squamous cell carcinoma(HNSCC):preliminary results from a single-arm,phase 2 study[J].Ann Oncol,2017,28(suppl 5):1-7.
26 Bahleda R,Braiteh FS,Balmanoukian AS,et al.Logn-term safety and clinical outcomes of atezolizumab in head and neck cancer:phase ia trial results[J].Ann Oncol,2017,28(Suppl 5):372-394.
27 Colevas AD,Bahleda R,Braiteh F,et al.Safety and clinical activity of atezolizumab in head and neck cancer:results from a phase I trial[J].Ann Oncol,2018,29(11):2247-2253.
28 Tang X,Chen S,Sui Q,et al.Response to nivolumab combining radiotherapy and nimotuzumab in metastatic oral squamous cell carcinoma patient with strong PD-L1 expression:a case report[J].Ann Transl Med,2020,8(6):402.
29 Siu LL,Even C,Mesía R,et al.Safety and efficacy of durvalumab with or without tremelimumab in patients with PD-L1-low/negative recurrent or metastatic HNSCC:The phase 2 CONDOR randomized clinical trial[J].JAMA Oncol,2019,5(2):195-203.
30 Ferris RL,Haddad R,Even C,et al.Durvalumab with or without tremelimumab in patients with recurrent or metastatic head and neck squamous cell carcinoma:EAGLE,a randomized,open-label phase III study[J].Ann Oncol,2020,31(7):942-950.
31 Poonia M,Ramalingam K,Goyal S,et al.Nanotechnology in oral cancer:A comprehensive review[J].J Oral Maxillofac Pathol,2017,21(3):407-414.
32 Madhulaxmi M,Iyer K,Periasamy R,et al.Role of cisplatin in oral squamous cell carcinoma-a review[J].J Adv Pharm Educ Res,2017,7:39-42.
33 Lucky SS,Idris NM,Huang K,et al.In vivo biocompatibility,biodistribution and therapeutic efficiency of titania coated upconversion nanoparticles for photodynamic therapy of solid oral cancers[J].Theranostics,2016,6(11):1844-1865.
34 Marcazzan S,Varoni EM,Blanco E,et al.Nanomedicine,an emerging therapeutic strategy for oral cancer therapy[J].Oral Oncol,2018,76:1-7.
35 Li X,Li L,Huang Y,et al.Synergistic therapy of chemotherapeutic drugs and MTH1 inhibitors using a pH-sensitive polymeric delivery system for oral squamous cell carcinoma[J].Biomater Sci,2017,5(10):2068-2078.
36 Wang J,Xie T,Wang B,et al.PD-1 blockade prevents the development and progression of carcinogen-induced oral premalignant lesions[J].Cancer Prev Res(Phila),2017,10(12):684-693.
37 Russo D,Merolla F,Mascolo M,et al.FKBP51 immunohistochemical expression:A new prognostic biomarker for OSCC[J].Int J Mol Sci,2017,18(2):443.
38 Emami N,Mohamadnia A,Mirzaei M,et al.MiR-155,miR-191,and miR-494 as diagnostic biomarkers for oral squamous cell carcinoma and the effects of avastin on these biomarkers[J].J Korean Assoc Oral Maxillofac Surg,2020,46(5):341-347.
39 Chang Y,Tolani B,Nie X,et al.Review of the clinical applications and technological advances of circulating tumor DNA in cancer monitoring[J].Ther Clin Risk Manag,2017,13:1363-1374.
40 Chalmers ZR,Connelly CF,Fabrizio D,et al.Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden[J].Genome Med,2017,9(1):34.
41 Carbone DP,Reck M,Paz-Ares L,et al.First-line nivolumab in stage IV or recurrent non-small-cell lung cancer[J].N Engl J Med,2017,376(25):2415-2426.

[1]	杨开炎, 韦永昌, 杨秋云, 唐凤珠. 鼻咽癌的免疫治疗研究进展[J]. 实用肿瘤学杂志, 2021, 35(6): 542-546.
[2]	卢俊蓉, 王惠文, 何东风. SALL4高表达在食管鳞癌临床病理及预后判定中的意义[J]. 实用肿瘤学杂志, 2021, 35(5): 420-425.
[3]	张伟明, 孙坚萍, 赵艳. 共刺激受体:肿瘤免疫疗法的潜在靶点[J]. 实用肿瘤学杂志, 2021, 35(5): 441-446.
[4]	汪叶, 尚乃舰. 影像组学在非小细胞肺癌诊疗中的应用进展[J]. 实用肿瘤学杂志, 2021, 35(5): 485-488.
[5]	熊巍, 王丹, 王瑾晖, 张颖, 曹冬焱. 中性粒细胞/淋巴细胞比值在外阴鳞癌和外阴上皮内瘤变筛查中的预测价值[J]. 实用肿瘤学杂志, 2021, 35(2): 125-130.
[6]	王明明, 陈晓品. 抗PD-1/PD-L1和CTLA-4免疫治疗在头颈鳞癌中的研究进展[J]. 实用肿瘤学杂志, 2021, 35(2): 179-183.
[7]	张璐,陆静钰(综述),陆海军(审校). 头颈部鳞癌相关生物标志物与免疫治疗预后的关系[J]. 实用肿瘤学杂志, 2021, 35(1): 55-58.
[8]	林映羲, 龙雅怡, 傅俊宏, 刘芳, 陈敏敏. 单核/巨噬细胞在非霍奇金淋巴瘤中的研究进展[J]. 实用肿瘤学杂志, 2020, 34(4): 352-356.
[9]	张连齐, 李吉辰, 朴松林, 赛音乌力吉, 元冬梅, 沈禹辰. PD-L1与MTA1在口腔鳞癌中的表达与临床意义[J]. 实用肿瘤学杂志, 2020, 34(3): 220-224.
[10]	王璞, 韦丽宾, 倪广晓. CCNB1基因通过调控PI3K/Akt信号通路对口腔鳞癌细胞增殖、侵袭和迁移的影响[J]. 实用肿瘤学杂志, 2020, 34(2): 144-149.
[11]	李磊 , 张清媛. 乳腺癌抗肿瘤血管治疗的临床进展[J]. 实用肿瘤学杂志, 2019, 33(5): 461-465.
[12]	徐文品, 焦琨(综述), 张伟(审校). 长链非编码RNAs在口腔鳞癌中的研究进展[J]. 实用肿瘤学杂志, 2018, 32(3): 258-262.
[13]	段艳军, 徐卫, 陈文杰, 王凤娟. Wnt通路抑制剂ETC-159处理对口腔鳞癌细胞增殖迁移的影响[J]. 实用肿瘤学杂志, 2018, 32(2): 103-106.
[14]	张群综述，李多杰审校. PD-1/PD-L1在食管鳞癌中的研究进展[J]. 实用肿瘤学杂志, 2017, 31(3): 250-253.
[15]	周士祥，综述，李多杰，审校. 锌离子转运体LIV-1在食管鳞癌中的研究进展[J]. 实用肿瘤学杂志, 2016, 30(6): 572-576.