晚期非小细胞肺癌免疫治疗进展

张志敏; 章必成; 许斌; 宋启斌

doi:10.3981/j.issn.1000-7857.2023.18.005

PDF(628 KB)

科技导报 ›› 2023, Vol. 41 ›› Issue (18) : 36-42. DOI: 10.3981/j.issn.1000-7857.2023.18.005

专题：癌症防治

晚期非小细胞肺癌免疫治疗进展

作者信息 -

武汉大学人民医院肿瘤中心，武汉 430060

作者简介:

张志敏，副主任医师，研究方向为肿瘤DNA损伤修复与肿瘤耐药机制，电子信箱：zzm7908@whu.edu.cn

The current and future road of immunotherapy for advanced non- small cell lung cancer

Author information -

Cancer Center, Renmin Hospital of Wuhan University, Wuhan 430060, China

摘要

免疫治疗作为目前最具影响力的肿瘤治疗手段，已全面改变晚期非小细胞肺癌（non-small cell lung cancer，NSCLC）的治疗格局。综述了晚期NSCLC免疫治疗存在的诸多尚待解决的问题，如免疫联合治疗模式的组合和优化、免疫治疗耐药的机制和应对策略、寻找合适的免疫治疗相关生物标志物、特殊人群特征的免疫治疗以及免疫治疗相关毒性管理等。探讨了晚期NSCLC免疫治疗的现状和未来之路。

Abstract

Immunotherapy, as the most influential tumor treatment method at present, has comprehensively changed the treatment pattern of advanced non-small cell lung cancer (NSCLC). However, there are still many unresolved issues in the immunotherapy of advanced NSCLC, such as the combination and optimization of immunotherapy combination models, the mechanism and response strategies of resistance in tumor immunotherapy, finding effective biomarkers for immunotherapy, exploring immunotherapy strategies with special population characteristics, and managing the toxic side effects of immunotherapy. This article proposes some issues and perspectives on the current status and future path of immunotherapy for advanced NSCLC, hoping to provide new ideas that are in line with the current immunotherapy for advanced NSCLC, and to provide readers with directions for thinking and future exploration.

导出引用

张志敏, 章必成, 许斌, 宋启斌. 晚期非小细胞肺癌免疫治疗进展[J]. 科技导报, 2023, 41(18): 36-42 https://doi.org/10.3981/j.issn.1000-7857.2023.18.005

ZHANG Zhimin, ZHANG Bicheng, XU Bin, SONG Qibin. The current and future road of immunotherapy for advanced non- small cell lung cancer[J]. Science & Technology Review, 2023, 41(18): 36-42 https://doi.org/10.3981/j.issn.1000-7857.2023.18.005

参考文献

[1] Garon E B, Rizvi N A, Hui R, et al. Pembrolizumab for the treatment of non-small-cell lung cancer[J]. The New England Journal of Medicine, 2015, 372(21): 2018-2028.
[2] Reck M, Rodrí guez-Abreu D, Robinson A G, et al. Fiveyear outcomes with pembrolizumab versus chemotherapy for metastatic non-small-cell lung cancer with PD-L1 tumor proportion score≥50%[J]. Journal of Clinical Oncology, 2021, 39(21): 2339-2349.
[3] Mok T S K, Wu Y L, Kudaba I, et al. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): A randomised, open-label, controlled, phase 3 trial [J]. The Lancet, 2019, 393(10183): 1819-1830.
[4] 付烊, 朱波, 章必成 . 晚期肺癌免疫治疗的现状与未来[J]. 医药导报, 2019, 38(8): 4.
[5] Herrera F G, Bourhis J, Coukos G. Radiotherapy combination opportunities leveraging immunity for the next oncology practice[J]. CA-A Cancer Journal for Clinicians, 2017, 67(1): 65-85.
[6] Socinski M A, Nishio M, Jotte R M, et al. IMpower150 final overall survival analyses for atezolizumab plus bevacizumab and chemotherapy in first-line metastatic nonsquamous NSCLC[J]. Journal of Thoracic Oncology, 2021, 16(11): 1909-1924.
[7] Naoki F, Satoshi W, Atsushi N, et al. A phase 2 study of atezolizumab (atezo) plus bevacizumab (bev) plus carboplatin (carbo) plus paclitaxel (pac; ABCP) for previously treated patients with NSCLC harboring EGFR mutations (EGFRm) [C]//2022 ASCO Annual Meeting. Chicago, USA: Journal of Clinical Oncology, 2022.
[8] Paz-Ares L, Ciuleanu T E, 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 Oncology, 2021, 22(2): 198-211.
[9] Brahmer J R, Lee J S, Ciuleanu T E, et al. Five-year survival outcomes with nivolumab plus ipilimumab versus chemotherapy as first-line treatment for metastatic non-small-cell lung cancer in checkmate 227[J]. Journal of Clinical Oncology, 2023, 41(6): 1200-1212.
[10] Goto Y , Su W C, Benjamin P L, et al. TROPION-Lung02: Datopotamab deruxtecan (Dato-DXd) plus pembrolizumab (pembro) with or without platinum chemotherapy (Pt-CT) in advanced non-small cell lung cancer (aNSCLC) [C]//ASCO Annual Meeting 2023. Chicago, USA: Journal of Clinical Oncology, 2023.
[11] Creelan B C, Wang C, Teer J K, et al. Tumor-infiltrating lymphocyte treatment for anti-PD-1-resistant metastatic lung cancer: A phase 1 trial[J]. Nature Medicine, 2021, 27(8): 1410-1418.
[12] Kim C G, Kim K H, Pyo K H, et al. Hyperprogressive disease during PD-1/PD-L1 blockade in patients with non-small-cell lung cancer[J]. Annals of Oncology, 2019, 30(7): 1104-1113.
[13] 朱波. 肿瘤免疫治疗耐药机制与克服策略[J]. 中国肿瘤生物治疗杂志, 2023, 30(3): 187-195.
[14] Nie J, Wang C M, Liu Y, et al. Addition of low-dose decitabine to anti-PD-1 antibody camrelizumab in relapsed/refractory classical Hodgkin lymphoma[J]. Journal of Clinical Oncology, 2019, 37(17): 1479-1489.
[15] Ribas A, Medina T, Kummar S, et al. SD-101 in combination with pembrolizumab in advanced melanoma: Results of a phaseⅠb, multicenter study[J]. Cancer Discovery, 2018, 8(10): 1250-1257.
[16] Ni K Y, Luo T K, Lan G X, et al. A nanoscale metal-organic framework to mediate photodynamic therapy and deliver CpG oligodeoxynucleotides to enhance antigen presentation and cancer immunotherapy[J]. Angewandte Chemie International Edition, 2020, 59(3): 1108-1112.
[17] Kawashima S, Inozume T, Kawazu M, et al. TIGIT/CD155 axis mediates resistance to immunotherapy in patients with melanoma with the inflamed tumor microenvironment[J]. Journal for Immunotherapy of Cancer, 2021, 9(11): e003134.
[18] Bockorny B, Semenisty V, Macarulla T, et al. BL-8040, a CXCR4 antagonist, in combination with pembrolizumab and chemotherapy for pancreatic cancer: The COMBAT trial[J]. Nature Medicine, 2020, 26(6): 878-885.
[19] Flores-toro J A, Luo D F, Gopinath A, et al. CCR2 inhibition reduces tumor myeloid cells and unmasks a checkpoint inhibitor effect to slow progression of resistant murine gliomas[J]. Proceedings of the National Academy of Sciences of the United States of America, 2020, 117(2): 1129-1138.
[20] Vargas F A, Furnessaj S, Solomon I, et al. Fc-optimized anti-CD25 depletes tumor-infiltrating regulatory T cells and synergizes with PD-1 blockade to eradicate established tumors[J]. Immunity, 2017, 46 (4): 577-586.
[21] Cannarile M A , Weisser M , Jacob W , et al. Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy[J]. Journal for Immunotherapy of Cancer, 2017, 5(1): 53
[22] Mariathasan S, Turley S J, Nickles D, et al. TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells[J]. Nature, 2018, 554(7693): 544-548.
[23] Miron B, Geynisman D M. Bempegaldesleukin/nivolumab and challenges in first-line treatment of metastatic urothelial carcinoma[J]. European Urology, 2022, 82(4): 374-376.
[24] Kurz E, Hirsch C A, Dalton T, et al. Exercise-induced engagement of the IL-15/IL-15Rα axis promotes anti-tumor immunity in pancreatic cancer[J]. Cancer Cell, 2022, 40(7): 720-737.
[25] Davar D, Dzutsev A K, Mcculloch J A, et al. Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients[J]. Science, 2021, 371(6529): 595-602.
[26] Vokes N I, Gandara D R, Sezer A, et al. Circulating tumor DNA (ctDNA) dynamics and survival outcomes in patients (pts) with advanced non-small cell lung cancer (aNSCLC) and high (>50%) programmed cell death-ligand 1 (PD-L1) expression, randomized to cemiplimab(cemi) vs chemotherapy (chemo)[C]//ASCO Annual Meeting 2023. Chicago, USA: Journal of Clinical Oncology, 2023.
[27] Sánchez-Magraner L, Gumuzio J, Miles J, et al. Functional engagement of the PD-1/PD-L1 complex but not PD-L1 expression is highly predictive of patient response to immunotherapy in non-small-cell lung cancer[J]. Journal of Clinical Oncology, 2023, 41(14): 2561-2570.
[28] Lichtenstein M R L, Nipp R D, Muzikansky A, et al. Impact of age on outcomes with immunotherapy in patients with non-small cell lung cancer[J]. Journal of Thoracic Oncology, 2019, 14(3): 547-552.
[29] Uematsu M, Tsukita Y, Tozuka T, et al. First-line immune checkpoint inhibitors alone or in combination with chemotherapy in real-life elderly patients with advanced non-small cell lung cancer (NEJ057) [C]//ASCO Annual Meeting 2023. Chicago, USA: Journal of Clinical Oncology, 2023.
[30] Yang J C, Lee D H, Lee J S, et al. Pemetrexed and platinum with or without pembrolizumab for tyrosine kinase inhibitor (TKI)-resistant, EGFR-mutant, metastatic nonsquamous NSCLC: Phase 3 KEYNOTE-789 study[C]//2023 ASCO Annual Meeting. Chicago, USA: Journal of Clinical Oncology, 2023.
[31] Lee A T M, Nagasaka M. CheckMate-722: The rise and fall of nivolumab with chemotherapy in TKI-refractory EGFR-mutant NSCLC[J]. Lung Cancer (Auckl), 2023, 14: 41-46.
[32] Lu S, Wu L, Jian H, et al. Sintilimab plus bevacizumab biosimilar IBI305 and chemotherapy for patients with EGFR-mutated non-squamous non-small-cell lung cancer who progressed on EGFR tyrosine-kinase inhibitor therapy (ORIENT-31): First interim results from a randomised, double-blind, multicentre, phase 3 trial[J]. Lancet Oncology, 2022, 23(9): 1167-1179.
[33] Champiat S, Lambotte O, Barreau E, et al. Management of immune checkpoint blockade dysimmune toxicities: A collaborative position paper[J]. Annals of Oncology, 2016, 27(4): 559-574.
[34] 中国临床肿瘤学会(CSCO)免疫治疗专家委员会 . 免疫检查点抑制剂相关的毒性管理指南[M]. 北京: 人民卫生出版社, 2023.