肿瘤内异质性在转移性非小细胞肺癌对免疫检查点抑制剂反应中的作用
The Role of Intratumor Heterogeneity in the Response of Metastatic Non-Small Cell Lung Cancer to Immune Checkpoint Inhibitors.
作者信息
Nicoś Marcin, Krawczyk Paweł, Crosetto Nicola, Milanowski Janusz
机构信息
Department of Pneumonology, Oncology and Allergology, Medical University of Lublin, Lublin, Poland.
Science for Life Laboratory, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
出版信息
Front Oncol. 2020 Dec 4;10:569202. doi: 10.3389/fonc.2020.569202. eCollection 2020.
Abstract
Immune checkpoint inhibitors (ICIs) represent one of the most promising therapeutic approaches in metastatic non-small cell lung cancer (M-NSCLC). Unfortunately, approximately 50-75% of patients do not respond to this treatment modality. Intratumor heterogeneity (ITH) at the genetic and phenotypic level is considered as a major cause of anticancer therapy failure, including resistance to ICIs. Recent observations suggest that spatial heterogeneity in the composition and spatial organization of the tumor microenvironment plays a major role in the response of M-NSCLC patients to ICIs. In this mini review, we first present a brief overview of the use of ICIs in M-NSCLC. We then discuss the role of genetic and non-genetic ITH on the efficacy of ICIs in patients with M-NSCLC.
摘要
免疫检查点抑制剂（ICIs）是转移性非小细胞肺癌（M-NSCLC）中最有前景的治疗方法之一。不幸的是，约50-75%的患者对这种治疗方式无反应。遗传和表型水平的肿瘤内异质性（ITH）被认为是抗癌治疗失败的主要原因，包括对ICIs的耐药性。最近的观察表明，肿瘤微环境的组成和空间组织中的空间异质性在M-NSCLC患者对ICIs的反应中起主要作用。在本综述中，我们首先简要概述ICIs在M-NSCLC中的应用。然后我们讨论遗传和非遗传ITH对M-NSCLC患者ICIs疗效的作用。
相似文献
1
The Role of Intratumor Heterogeneity in the Response of Metastatic Non-Small Cell Lung Cancer to Immune Checkpoint Inhibitors.肿瘤内异质性在转移性非小细胞肺癌对免疫检查点抑制剂反应中的作用
Front Oncol. 2020 Dec 4;10:569202. doi: 10.3389/fonc.2020.569202. eCollection 2020.
2
PD-1/PD-L1 Blockade Therapy in Advanced Non-Small-Cell Lung Cancer: Current Status and Future Directions.PD-1/PD-L1 阻断疗法在晚期非小细胞肺癌中的应用：现状与未来方向。
Oncologist. 2019 Feb;24(Suppl 1):S31-S41. doi: 10.1634/theoncologist.2019-IO-S1-s05.
3
Immune Checkpoint Inhibitors (ICIs) in Non-Small Cell Lung Cancer (NSCLC).非小细胞肺癌（NSCLC）中的免疫检查点抑制剂（ICIs）。
J UOEH. 2018;40(2):173-189. doi: 10.7888/juoeh.40.173.
4
Epidermal Growth Factor Receptor (EGFR) Pathway, Yes-Associated Protein (YAP) and the Regulation of Programmed Death-Ligand 1 (PD-L1) in Non-Small Cell Lung Cancer (NSCLC).表皮生长因子受体（EGFR）通路、Yes 相关蛋白（YAP）与非小细胞肺癌（NSCLC）中程序性死亡配体 1（PD-L1）的调控。
Int J Mol Sci. 2019 Aug 5;20(15):3821. doi: 10.3390/ijms20153821.
5
Efficacy of Immune Checkpoint Inhibitors in KRAS-Mutant Non-Small Cell Lung Cancer (NSCLC).免疫检查点抑制剂在 KRAS 突变型非小细胞肺癌（NSCLC）中的疗效。
J Thorac Oncol. 2019 Jun;14(6):1095-1101. doi: 10.1016/j.jtho.2019.01.011. Epub 2019 Feb 6.
6
Association of Survival and Immune-Related Biomarkers With Immunotherapy in Patients With Non-Small Cell Lung Cancer: A Meta-analysis and Individual Patient-Level Analysis.免疫治疗与非小细胞肺癌患者生存及免疫相关生物标志物的相关性：一项荟萃分析和个体患者水平分析。
JAMA Netw Open. 2019 Jul 3;2(7):e196879. doi: 10.1001/jamanetworkopen.2019.6879.
7
Predictive Biomarkers of Response to Immunotherapy in Metastatic Renal Cell Cancer.转移性肾细胞癌免疫治疗反应的预测生物标志物
Front Oncol. 2020 Aug 12;10:1644. doi: 10.3389/fonc.2020.01644. eCollection 2020.
8
Circulating Tumor Cell PD-L1 Expression as Biomarker for Therapeutic Efficacy of Immune Checkpoint Inhibition in NSCLC.循环肿瘤细胞 PD-L1 表达作为 NSCLC 免疫检查点抑制治疗疗效的生物标志物。
Cells. 2019 Aug 1;8(8):809. doi: 10.3390/cells8080809.
9
Immunotherapy in the First-Line Treatment of NSCLC: Current Status and Future Directions in China.中国非小细胞肺癌一线治疗中的免疫疗法：现状与未来方向
Front Oncol. 2021 Nov 25;11:757993. doi: 10.3389/fonc.2021.757993. eCollection 2021.
10
Immune checkpoint blockade as a potential therapeutic target in non-small cell lung cancer.免疫检查点阻断作为非小细胞肺癌的潜在治疗靶点。
Expert Opin Biol Ther. 2016 Oct;16(10):1209-23. doi: 10.1080/14712598.2016.1214265. Epub 2016 Aug 5.
引用本文的文献
1
Sequentially Activated Smart DNA Nanospheres for Photoimmunotherapy and Immune Checkpoint Blockade.用于光免疫疗法和免疫检查点阻断的顺序激活智能DNA纳米球
Adv Sci (Weinh). 2025 Jan;12(3):e2410632. doi: 10.1002/advs.202410632. Epub 2024 Nov 26.
2
Novel strategies for modulating the gut microbiome for cancer therapy.用于癌症治疗的调节肠道微生物组的新策略。
Adv Drug Deliv Rev. 2024 Jul;210:115332. doi: 10.1016/j.addr.2024.115332. Epub 2024 May 15.
3
DNA damage response-related immune activation signature predicts the response to immune checkpoint inhibitors: from gastrointestinal cancer analysis to pan-cancer validation.DNA 损伤反应相关免疫激活特征可预测免疫检查点抑制剂的反应：从胃肠道癌症分析到泛癌验证。
Cancer Biol Med. 2023 Dec 29;21(3):252-66. doi: 10.20892/j.issn.2095-3941.2023.0303.
4
Dynamical modeling of proliferative-invasive plasticity and IFNγ signaling in melanoma reveals mechanisms of PD-L1 expression heterogeneity.黑色素瘤增殖-侵袭可塑性和 IFNγ 信号的动力学建模揭示了 PD-L1 表达异质性的机制。
J Immunother Cancer. 2023 Sep;11(9). doi: 10.1136/jitc-2023-006766.
5
Dynamical modelling of proliferative-invasive plasticity and IFNγ signaling in melanoma reveals mechanisms of PD-L1 expression heterogeneity.黑色素瘤中增殖侵袭可塑性和IFNγ信号传导的动力学模型揭示了PD-L1表达异质性的机制。
bioRxiv. 2023 Jun 12:2023.01.09.523355. doi: 10.1101/2023.01.09.523355.
6
Evaluation of Blood Tumor Mutation Burden for the Efficacy of Second-Line Atezolizumab Treatment in Non-Small Cell Lung Cancer: BUDDY Trial.评估二线阿替利珠单抗治疗非小细胞肺癌的疗效的血液肿瘤突变负担：BUDDY 试验。
Cells. 2023 Apr 25;12(9):1246. doi: 10.3390/cells12091246.
7
Accumulation of STR-Loci Aberrations in Subclones of Jurkat Cell Line as a Model of Tumor Clonal Evolution.STR 基因座异常在 Jurkat 细胞系亚克隆中的积累作为肿瘤克隆进化的模型。
Genes (Basel). 2023 Feb 24;14(3):571. doi: 10.3390/genes14030571.
8
Novel Genetic Subtypes of Urothelial Carcinoma With Differential Outcomes on Immune Checkpoint Blockade.新型尿路上皮癌遗传亚型对免疫检查点阻断具有不同的疗效。
J Clin Oncol. 2023 Jun 10;41(17):3225-3235. doi: 10.1200/JCO.22.02144. Epub 2023 Mar 16.
9
Lung Cancer Immunotherapy: Beyond Common Immune Checkpoints Inhibitors.肺癌免疫疗法：超越常见免疫检查点抑制剂
Cancers (Basel). 2022 Dec 13;14(24):6145. doi: 10.3390/cancers14246145.
10
Transcriptional Heterogeneity of Cellular Senescence in Cancer.肿瘤细胞衰老的转录异质性。
Mol Cells. 2022 Sep 30;45(9):610-619. doi: 10.14348/molcells.2022.0036. Epub 2022 Aug 19.
本文引用的文献
1
Programmed Death-Ligand 1 Heterogeneity and Its Impact on Benefit From Immune Checkpoint Inhibitors in NSCLC.程序性死亡配体 1 异质性及其对 NSCLC 免疫检查点抑制剂获益的影响。
J Thorac Oncol. 2020 Sep;15(9):1449-1459. doi: 10.1016/j.jtho.2020.04.026. Epub 2020 May 8.
2
Single-cell RNA sequencing demonstrates the molecular and cellular reprogramming of metastatic lung adenocarcinoma.单细胞 RNA 测序显示转移性肺腺癌的分子和细胞重编程。
Nat Commun. 2020 May 8;11(1):2285. doi: 10.1038/s41467-020-16164-1.
3
Single-Cell Approaches to Profile the Response to Immune Checkpoint Inhibitors.单细胞方法分析免疫检查点抑制剂的反应。
Front Immunol. 2020 Mar 20;11:490. doi: 10.3389/fimmu.2020.00490. eCollection 2020.
4
New advances in antiangiogenic combination therapeutic strategies for advanced non-small cell lung cancer.晚期非小细胞肺癌抗血管生成联合治疗策略的新进展。
J Cancer Res Clin Oncol. 2020 Mar;146(3):631-645. doi: 10.1007/s00432-020-03129-6. Epub 2020 Feb 17.
5
Inter-tumor heterogeneity of PD-L1 expression in non-small cell lung cancer.非小细胞肺癌中PD-L1表达的肿瘤间异质性。
J Thorac Dis. 2019 Dec;11(12):4982-4991. doi: 10.21037/jtd.2019.12.24.
6
A signature of tumor immune microenvironment genes associated with the prognosis of non‑small cell lung cancer.与非小细胞肺癌预后相关的肿瘤免疫微环境基因特征
Oncol Rep. 2020 Mar;43(3):795-806. doi: 10.3892/or.2020.7464. Epub 2020 Jan 14.
7
Comprehensive T cell repertoire characterization of non-small cell lung cancer.非小细胞肺癌的全面 T 细胞受体谱特征。
Nat Commun. 2020 Jan 30;11(1):603. doi: 10.1038/s41467-019-14273-0.
8
Spatial heterogeneity of the T cell receptor repertoire reflects the mutational landscape in lung cancer.T 细胞受体库的空间异质性反映了肺癌中的突变景观。
Nat Med. 2019 Oct;25(10):1549-1559. doi: 10.1038/s41591-019-0592-2. Epub 2019 Oct 7.
9
Small molecule immunomodulation: the tumor microenvironment and overcoming immune escape.小分子免疫调节：肿瘤微环境与克服免疫逃逸。
J Immunother Cancer. 2019 Aug 22;7(1):224. doi: 10.1186/s40425-019-0667-0.
10
Tumor mutation burden: from comprehensive mutational screening to the clinic.肿瘤突变负荷：从全面的突变筛查到临床应用
Cancer Cell Int. 2019 Aug 7;19:209. doi: 10.1186/s12935-019-0929-4. eCollection 2019.
Zotero 插件