非小细胞肺癌免疫检查点抑制剂治疗进展

王硕; 邓云天; 彭欢; 张向峰

doi:10.12290/xhyxzz.2022-0151

非小细胞肺癌免疫检查点抑制剂治疗进展

doi: 10.12290/xhyxzz.2022-0151

王硕¹,
邓云天¹,
彭欢¹,
张向峰^2, ,

1.
重庆医科大学第一临床学院，重庆 400016
2.
首都医科大学附属北京安贞医院呼吸与危重症科，北京 100029

详细信息

通讯作者:
张向峰, E-mail：xfzh20008@163.com

中图分类号: R734; R453
计量
- 文章访问数: 275
- HTML全文浏览量: 31
- PDF下载量: 65
- 被引次数: 0
出版历程
- 收稿日期: 2022-03-26
- 录用日期: 2022-05-27
- 网络出版日期: 2022-08-09
- 刊出日期: 2023-03-30

Progress in the Treatment of Non-small Cell Lung Cancer with Immune Checkpoint Inhibitors

1.
First Clinical College, Chongqing Medical University, Chongqing 400016, China
2.
Pulmonary and Critical Care Medicine, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China

More Information

Corresponding author: ZHANG Xiangfeng, E-mail: xfzh20008@163.com

摘要

摘要: 肺癌是全球范围内发病率及死亡率极高的恶性肿瘤，其中以非小细胞肺癌(non-small cell lung cancer，NSCLC)最为常见。NSCLC的传统治疗主要依靠化学药物，近年来免疫治疗成为NSCLC治疗的热点，并取得了令人瞩目的进展。大量新型生物免疫制剂被开发并应用于临床，其中免疫检查点抑制剂的应用最广、疗效最为肯定。本文将对近年NSCLC免疫治疗生物标志物研究现状及进展进行阐述，以期提高免疫治疗精准度，更好地指导NSCLC患者的个体化治疗。
- 非小细胞肺癌 /
- 免疫治疗 /
- CTLA-4 /
- PD-1 /
- PD-L1
Abstract: Lung cancer is a malignant tumor with high incidence rate and mortality worldwide. Non-small cell lung cancer (NSCLC) is the most common malignancy. The traditional treatment of NSCLC mainly depends on chemical drugs. In recent years, immunotherapy has become a hot spot in the treatment of NSCLC and made remarkable progress. The overall objective remission rate of immunotherapy for NSCLC patients is about 20%. A large number of new biological immune agents have been developed and applied in clinic. Among them, immune checkpoint inhibitor (ICI) has the widest application and the most positive effect on NSCLC. This paper summarizes the research status and progress of immunotherapy biomarkers of NSCLC in recent years, with the hope of improving the accuracy of immunotherapy and better guiding individualized treatment of NSCLC patients.
- non-small cell lung cancer /
- immunotherapy /
- CTLA-4 /
- PD-1 /
- PD-L1
注释:

作者贡献：王硕负责文献检索、论文撰写及修订；邓云天、彭欢负责论文选题及修订；张向峰负责论文审校。

利益冲突：所有作者均声明不存在利益冲突

HTML全文

参考文献(64)

[1]	Garon EB, Rizvi NA, Hui RN, et al. Pembrolizumab for the Treatment of Non-small-cell Lung Cancer[J]. N Engl J Med, 2015, 372: 2018-2028. doi: 10.1056/NEJMoa1501824
[2]	Brahmer J, Reckamp KL, Baas P, et al. Nivolumab Versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer[J]. N Engl J Med, 2015, 373: 123-135. doi: 10.1056/NEJMoa1504627
[3]	江昌, 易玲, 高翔, 等. 非小细胞肺癌免疫治疗生物标志物研究进展[J]. 中国肺癌杂志, 2022, 25: 46-53. https://www.cnki.com.cn/Article/CJFDTOTAL-FAIZ202201006.htm Jiang C, Yi L, Gao X, et al. Research Progress of Immunotherapy Biomarkers for Non-small Cell Lung Cancer[J]. Zhongguo Feiai Zazhi, 2022, 25: 46-53. https://www.cnki.com.cn/Article/CJFDTOTAL-FAIZ202201006.htm
[4]	Reck M, Ciuleanu TE, Cobo M, et al. First-line Nivolumab Plus Ipilimumab With Two Cycles of Chemotherapy Versus Chemotherapy Alone (Four Cycles) in Advanced Non-small-cell Lung Cancer: CheckMate 9LA 2-year Update[J]. ESMO Open, 2021, 6: 100273. doi: 10.1016/j.esmoop.2021.100273
[5]	Reck M, Rodríguez-Abreu D, Robinson AG, et al. Pembrolizumab Versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer[J]. N Engl J Med, 2016, 375: 1823-1833. doi: 10.1056/NEJMoa1606774
[6]	Pardoll DM. The Blockade of Immune Checkpoints in Cancer Immunotherapy[J]. Nat Rev Cancer, 2012, 12: 252-264. doi: 10.1038/nrc3239
[7]	Tekguc M, Wing JB, Osaki M, et al. Treg-expressed CTLA-4 Depletes CD80/CD86 by Trogocytosis, Releasing Free PD-L1 on Antigen-presenting Cells[J]. Proc Natl Acad Sci U S A, 2021, 118: e2023739118. doi: 10.1073/pnas.2023739118
[8]	Morad G, Helmink BA, Sharma P, et al. Hallmarks of Response, Resistance, and Toxicity to Immune Checkpoint Blockade[J]. Cell, 2021, 184: 5309-5337. doi: 10.1016/j.cell.2021.09.020
[9]	Reck M, Rodríguez-Abreu D, Robinson AG, et al. Five-Year Outcomes With Pembrolizumab Versus Chemotherapy for Metastatic Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score ≥ 50[J]. J Clin Oncol, 2021, 39: 2339-2349. doi: 10.1200/JCO.21.00174
[10]	Ma CL, Sun X, Shen D, et al. Ectopic Expression of LAG-3 in non-Small-cell Lung Cancer Cells and Its Clinical Significance[J]. J Clin Lab Anal, 2020, 34: e23244.
[11]	Datar I, Sanmamed MF, Wang J, et al. Expression Analysis and Significance of PD-1, LAG-3, and TIM-3 in Human Non-Small Cell Lung Cancer Using Spatially Resolved and Multiparametric Single-Cell Analysis[J]. Clin Cancer Res, 2019, 25: 4663-4673. doi: 10.1158/1078-0432.CCR-18-4142
[12]	Ding L, Getz G, Wheeler DA, et al. Somatic Mutations Affect Key Pathways in Lung Adenocarcinoma[J]. Nature, 2008, 455: 1069-1075. doi: 10.1038/nature07423
[13]	Levin SD, Taft DW, Brandt CS, et al. Vstm3 Is a Member of the CD28 Family and an Important Modulator of T-cell Function[J]. Eur J Immunol, 2011, 41: 902-915. doi: 10.1002/eji.201041136
[14]	Stanietsky N, Rovis TL, Glasner A, et al. Mouse TIGIT Inhibits NK-cell Cytotoxicity Upon Interaction With PVR[J]. Eur J Immunol, 2013, 43: 2138-2150. doi: 10.1002/eji.201243072
[15]	Dardalhon V, Schubart AS, Reddy J, et al. CD226 Is Specifically Expressed on the Surface of Th1 Cells and Regulates Their Expansion and Effector Functions[J]. J Immunol, 2005, 175: 1558-1565. doi: 10.4049/jimmunol.175.3.1558
[16]	Ocaña-Guzman R. Torre-Bouscoulet L, Sada-Ovalle I. TIM-3 Regulates Distinct Functions in Macrophages[J]. Front Immunol, 2016, 7: 229.
[17]	Zhou KJ, Guo S, Tong S, et al. Immunosuppression of Human Adipose-Derived Stem Cells on T cell Subsets via the Reduction of NF-kappaB Activation Mediated by PD-L1/PD-1 and Gal-9/TIM-3 Pathways[J]. Stem Cells Dev, 2018, 27: 1191-1202. doi: 10.1089/scd.2018.0033
[18]	He YY, Yu H, Rozeboom L, et al. LAG-3 Protein Expression in Non-Small Cell Lung Cancer and Its Relationship with PD-1/PD-L1 and Tumor-Infiltrating Lymphocytes[J]. J Thorac Oncol, 2017, 12: 814-823. doi: 10.1016/j.jtho.2017.01.019
[19]	Wennerberg E, Mukherjee S, Spada S, et al. Expression of the mono-ADP-ribosyltransferase ART1 by Tumor Cells Mediates Immune Resistance in Non-small Cell Lung Cancer[J]. Sci Transl Med, 2022, 14: eabe8195. doi: 10.1126/scitranslmed.abe8195
[20]	Wiede F, Lu KH, Du X, et al. PTP1B Is an Intracellular Checkpoint that Limits T-cell and CAR T-cell Antitumor Immunity[J]. Cancer Discov, 2022, 12: 752-773. doi: 10.1158/2159-8290.CD-21-0694
[21]	Kuske M, Haist M, Jung T, et al. Immunomodulatory Properties of Immune Checkpoint Inhibitors-More than Boosting T-Cell Responses?[J]. Cancers (Basel), 2022, 14: 1710. doi: 10.3390/cancers14071710
[22]	Mao SQ, Zhou F, Liu YW, et al. ICI Plus Chemotherapy Prolonged Survival Over ICI Alone in Patients With Previously Treated Advanced NSCLC[J]. Cancer Immunol Immunother, 2022, 71: 219-228. doi: 10.1007/s00262-021-02974-9
[23]	Ma XT, Zhang YJ, Wang S, et al. Immune Checkpoint Inhibitor (ICI) Combination Therapy Compared to Monotherapy in Advanced Solid Cancer: a Systematic Review[J]. J Cancer, 2021, 12: 1318-1333. doi: 10.7150/jca.49174
[24]	Brueckl WM, Ficker JH, Zeitler G. Clinically Relevant Prognostic and Predictive Markers for Immune-checkpoint-inhibitor (ICI) Therapy in Non-small Cell Lung Cancer (NSCLC)[J]. BMC Cancer, 2020, 20: 1185. doi: 10.1186/s12885-020-07690-8
[25]	Paz-Ares L, Ciuleanu TE, Cobo M, et al. First-line Nivolumab Plus Ipilimumab Combined With Two Cycles of Chemotherapy in Patients With Non-small-cell Lung Cancer (CheckMate 9LA): an International, Randomised, Open-label, Phase 3 Trial[J]. Lancet Oncol, 2021, 22: 198-211. doi: 10.1016/S1470-2045(20)30641-0
[26]	Muto S, Inomata S, Yamaguchi H, et al. CTLA-4 Expression in Tumor-infiltrating Lymphocytes Is Irrelevant to PD-L1 Expression in NSCLC[J]. Anticancer Res, 2021, 41: 6267-6272. doi: 10.21873/anticanres.15447
[27]	Formenti SC, Rudqvist NP, Golden E, et al. Radiotherapy induces responses of lung cancer to CTLA-4 blockade[J]. Nat Med, 2018, 12: 1845-1851.
[28]	Lynch TJ, Bondarenko I, Luft A, et al. Ipilimumab in Combination With Paclitaxel and Carboplatin as First-line Treatment in Stage ⅢB/Ⅳ Non-small-cell Lung Cancer: Results From a Randomized, Double-blind, Multicenter Phase Ⅱ Study[J]. J Clin Oncol, 2012, 30: 2046-2054. doi: 10.1200/JCO.2011.38.4032
[29]	Jiang CJ, Zhang L, Xu XP, et al. Engineering a Smart Agent for Enhanced Immunotherapy Effect by Simultaneously Blocking PD-L1 and CTLA-4[J]. Adv Sci (Weinh), 2021, 8: e2102500. doi: 10.1002/advs.202102500
[30]	Zhou YX, Lin Z, Zhang XY, et al. First-line Treatment for Patients With Advanced Non-small Cell Lung Carcinoma and High PD-L1 Expression: Pembrolizumab or Pembrolizumab Plus Chemotherapy[J]. J Immunother Cancer, 2019, 7: 120. doi: 10.1186/s40425-019-0600-6
[31]	Nassabein R, Gaudreau PO, Belkaid W, et al. A Phase Ⅰ/Ⅱ Study of Pembrolizumab in Combination With Nab-paclitaxel in Patients With Unresectable Stage Ⅲ or Stage Ⅳ non Small-cell Lung Carcinoma (NSCLC)[J]. Cancer Treat Res Commun, 2021, 28: 100421. doi: 10.1016/j.ctarc.2021.100421
[32]	Incorvaia L, Fanale D, Badalamenti G, et al. Programmed Death Ligand 1 (PD-L1) as a Predictive Biomarker for Pembrolizumab Therapy in Patients with Advanced Non-Small-Cell Lung Cancer (NSCLC)[J]. Adv Ther, 2019, 36: 2600-2617. doi: 10.1007/s12325-019-01057-7
[33]	Leighl NB, Hellmann MD, Hui R, et al. Pembrolizumab in Patients With Advanced Non-small-cell Lung Cancer (KEYNOTE-001): 3-year Results From an Open-label, Phase 1 Study[J]. Lancet Respir Med, 2019, 7: 347-357. doi: 10.1016/S2213-2600(18)30500-9
[34]	Mansfield AS, Herbst RS, de Castro G, et al. Outcomes With Pembrolizumab Monotherapy in Patients With Programmed Death-Ligand 1-Positive NSCLC With Brain Metastases: Pooled Analysis of KEYNOTE-001, 010, 024, and 042[J]. JTO Clin Res Rep, 2021, 2: 100205.
[35]	Oki R, Hirakawa Y, Kimura H, et al. Renal Effects after Pembrolizumab Treatment for Non-small Cell Lung Carcinoma[J]. Intern Med, 2020, 59: 977-981. doi: 10.2169/internalmedicine.3928-19
[36]	Shionoya Y, Hirohashi Y, Takahashi H, et al. Possible Pseudo-progression of Non-small Cell Lung Carcinoma in a Patient With Clinical Hyper-progression Associated With Trousseau Syndrome Who Was Treated With Pembrolizumab: A Case Report[J]. Anticancer Res, 2021, 41: 3699-3706. doi: 10.21873/anticanres.15161
[37]	Brahmer JR, Govindan R, Anders RA, et al. The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of non-small cell lung cancer (NSCLC)[J]. J Immunother Cancer, 2018, 6: 75. doi: 10.1186/s40425-018-0382-2
[38]	Tobita S, Kinehara Y, Tamura Y, et al. Successful Continuous Nivolumab Therapy for Metastatic Non-small Cell Lung Cancer After Local Treatment of Oligometastatic Lesions[J]. Thorac Cancer, 2020, 11: 2357-2360. doi: 10.1111/1759-7714.13539
[39]	Figueiredo A, Almeida MA, Almodovar MT, et al. Real-world Data From the Portuguese Nivolumab Expanded Access Program (EAP) in Previously Treated Non Small Cell Lung Cancer (NSCLC)[J]. Pulmonology, 2020, 26: 10-17. doi: 10.1016/j.pulmoe.2019.06.001
[40]	Schmid S, Diem S, Li QY, et al. Organ-specific Response to Nivolumab in Patients With Non-small Cell Lung Cancer (NSCLC)[J]. Cancer Immunol Immunother, 2018, 67: 1825-1832. doi: 10.1007/s00262-018-2239-4
[41]	Hellmann MD, Paz-Ares L, Bernabe Caro R, et al. Nivolumab Plus Ipilimumab in Advanced Non-Small-Cell Lung Cancer[J]. N Engl J Med, 2019, 381: 2020-2031. doi: 10.1056/NEJMoa1910231
[42]	Paz-Ares LG, Ramalingam SS, Ciuleanu TE, et al. First-Line Nivolumab Plus Ipilimumab in Advanced NSCLC: 4-Year Outcomes From the Randomized, Open-Label, Phase 3 CheckMate 227 Part 1 Trial[J]. J Thorac Oncol, 2022, 17: 289-308. doi: 10.1016/j.jtho.2021.09.010
[43]	Vokes EE, Ready N, Felip E, et al. Nivolumab Versus Docetaxel in Previously Treated Advanced Non-small-cell Lung Cancer (CheckMate 017 and CheckMate 057): 3-year Update and Outcomes in Patients With Liver Metastases[J]. Ann Oncol, 2018, 29: 959-965. doi: 10.1093/annonc/mdy041
[44]	Naito T, Umemura S, Nakamura H, et al. Successful Treatment With Nivolumab for SMARCA4-deficient Non-small Cell Lung Carcinoma With a High Tumor Mutation Burden: a Case Report[J]. Thorac Cancer, 2019, 10: 1285-1288. doi: 10.1111/1759-7714.13070
[45]	Kim JS, Nam TS, Kim J, et al. Myasthenia Gravis and Myopathy After Nivolumab Treatment for Non-small Cell Lung Carcinoma: a Case Report[J]. Thorac Cancer, 2019, 10: 2045-2049. doi: 10.1111/1759-7714.13177
[46]	Antonia SJ, Villegas A, Daniel D, et al. Durvalumab After Chemoradiotherapy in Stage Ⅲ Non-Small-Cell Lung Cancer[J]. N Engl J Med, 2017, 377: 1919-1929. doi: 10.1056/NEJMoa1709937
[47]	Li DN, Lu WQ, Yang BW, et al. Atezolizumab Mono-therapy or Plus Chemotherapy in First-Line Treatment for Advanced Non-Small Cell Lung Cancer Patients: A Meta-Analysis[J]. Front Immunol, 2021, 12: 666909. doi: 10.3389/fimmu.2021.666909
[48]	Fehrenbacher L, Spira A, Ballinger M, et al. Atezoli-zumab Versus Docetaxel for Patients With Previously Treated Non-small-cell Lung Cancer (POPLAR): a Multicentre, Open-label, Phase 2 Randomised Controlled Trial[J]. Lancet, 2016, 387: 1837-1846. doi: 10.1016/S0140-6736(16)00587-0
[49]	Zhou Q, Chen M, Jiang O, et al. Sugemalimab Versus Placebo After Concurrent or Sequential Chemoradiotherapy in Patients With Locally Advanced, Unresectable, Stage Ⅲ Non-small-cell Lung Cancer in China (GEMSTONE-301): Interim Results of a Randomised, Double-blind, Multicentre, Phase 3 Trial[J]. Lancet Oncol, 2022, 23: 209-219. doi: 10.1016/S1470-2045(21)00630-6
[50]	Zhou CC, Wang ZP, Sun YP, et al. Sugemalimab Versus Placebo, in Combination With Platinum-based Chemotherapy, as First-line Treatment of Metastatic Non-small-cell Lung Cancer (GEMSTONE-302): Interim and Final Analyses of a Double-blind, Randomised, Phase 3 Clinical Trial[J]. Lancet Oncol, 2022, 23: 220-233. doi: 10.1016/S1470-2045(21)00650-1
[51]	Boyer M, Şendur MAN, Rodríguez-Abreu D, et al. Pembrolizumab Plus Ipilimumab or Placebo for Metastatic Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score ≥ 50%: Randomized, Double-Blind Phase Ⅲ KEYNOTE-598 Study[J]. J Clin Oncol, 2021, 39: 2327-2338. doi: 10.1200/JCO.20.03579
[52]	Zhou J, Yu X, Hou LK, et al. Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Remodels Tumor Microenvironment by Upregulating LAG-3 in Advanced Non-small-cell Lung Cancer[J]. Lung Cancer, 2021, 153: 143-149. doi: 10.1016/j.lungcan.2021.01.010
[53]	Anon. Tiragolumab Impresses in Multiple Trials[J]. Cancer Discov, 2020, 10: 1086-1087.
[54]	Houssaini MS, Damou M, Ismaili N. Advances in the Management of Non-small Cell Lung Cancer (NSCLC): A New Practice Changing Data From asco 2020 Annual Meeting[J]. Cancer Treat Res Commun, 2020, 25: 100239. doi: 10.1016/j.ctarc.2020.100239
[55]	Horvath L, Pircher A. ASCO 2020 Non-small Lung Cancer (NSCLC) Personal Highlights[J]. Memo, 2021, 14: 66-69. doi: 10.1007/s12254-020-00673-2
[56]	Niu J, Maurice-Dror C, Lee DH, et al. First-in-human Phase 1 Study of the anti-TIGIT Antibody Vibostolimab as Monotherapy or With Pembrolizumab for Advanced Solid Tumors, Including Non-small-cell Lung Cancer[J]. Ann Oncol, 2022, 33: 169-180. doi: 10.1016/j.annonc.2021.11.002
[57]	Anon. An Anti-TIGIT Antibody with a PD-1 Inhibitor Shows Promise in Solid Tumors[J]. Cancer Discov, 2022, 12: 14.
[58]	Gomes de Morais AL, Cerdá S, de Miguel M. New Checkpoint Inhibitors on the Road: Targeting TIM-3 in Solid Tumors[J]. Curr Oncol Rep, 2022, 24: 651-658. doi: 10.1007/s11912-022-01218-y
[59]	Curigliano G, Gelderblom H, Mach N, et al. Phase I/Ib Clinical Trial of Sabatolimab, an Anti-TIM-3 Antibody, Alone and in Combination with Spartalizumab, an Anti-PD-1 Antibody, in Advanced Solid Tumors[J]. Clin Cancer Res, 2021, 27: 3620-3629. doi: 10.1158/1078-0432.CCR-20-4746
[60]	Khunger M, Hernandez AV, Pasupuleti V, et al. Programmed Cell Death 1 (PD-1) Ligand (PD-L1) Expression in Solid Tumors As a Predictive Biomarker of Benefit From PD-1/PD-L1 Axis Inhibitors: A Systematic Review and Meta-Analysis[J]. JCO Precis Oncol, 2017, 1: 1-15.
[61]	Yun J, Lee SH, Kim SY, et al. Antitumor Activity of Amivantamab(JNJ-61186372), an EGFR-MET Bispecific Anti-body, in Diverse Models of EGFR Exon 20 Insertion-Driven NSCLC[J]. Cancer Discov, 2020, 10: 1194-1209. doi: 10.1158/2159-8290.CD-20-0116
[62]	Park K, Haura EB, Leighl NB, et al. Amivantamab in EGFR Exon 20 Insertion-Mutated Non-Small-Cell Lung Cancer Progressing on Platinum Chemotherapy: Initial Results From the CHRYSALIS Phase I Study[J]. J Clin Oncol, 2021, 39: 3391-3402. doi: 10.1200/JCO.21.00662
[63]	Syed YY. Amivantamab: First Approval[J]. Drugs, 2021, 81: 1349-1353. doi: 10.1007/s40265-021-01561-7
[64]	中国临床肿瘤学会指南工作委员会. 小细胞肺癌诊疗指南2021[M]. 北京: 人民卫生出版社, 2021.

施引文献

资源附件(0)

访问统计

点击查看大图

计量

文章访问数: 275
HTML全文浏览量: 31
PDF下载量: 65
被引次数: 0

姓名
邮箱
手机号码
标题
留言内容
验证码

地址：	北京市东城区帅府园1号北京协和医院老楼7号楼 3层302室《协和医学杂志》编辑部
电话：	010-69154261/4262
E - mail：	medj@pumch.cn mjpumch@126.com
期刊网站版权所有：	《协和医学杂志》编辑部京ICP备 11002662

留言板

非小细胞肺癌免疫检查点抑制剂治疗进展

doi: 10.12290/xhyxzz.2022-0151

通讯作者:
张向峰, E-mail：xfzh20008@163.com

计量

Progress in the Treatment of Non-small Cell Lung Cancer with Immune Checkpoint Inhibitors

Corresponding author: ZHANG Xiangfeng, E-mail: xfzh20008@163.com

计量

目录

留言板

非小细胞肺癌免疫检查点抑制剂治疗进展

doi: 10.12290/xhyxzz.2022-0151

通讯作者: 张向峰, E-mail：xfzh20008@163.com

计量

出版历程

Progress in the Treatment of Non-small Cell Lung Cancer with Immune Checkpoint Inhibitors

Corresponding author: ZHANG Xiangfeng, E-mail: xfzh20008@163.com

计量

出版历程

目录

通讯作者:
张向峰, E-mail：xfzh20008@163.com