一种用于克服非小细胞肺癌治疗中抗原异质性的多靶向 CAR-T 细胞平台
A Multi-Targeting Chimeric Antigen Receptor-T Cell Platform to Overcome Antigen Heterogeneity in the Treatment of Non-Small Cell Lung Cancer.
这些发现支持采用多靶点CAR-T 策略来应对NSCLC及可能其他实体瘤中的抗原异质性。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
空间分辨转录组学揭示具有成熟三级淋巴结构的 NSCLC 中对免疫治疗原发性耐药的决定因素
英文原题：Spatially resolved transcriptomics reveal the determinants of primary resistance to immunotherapy in NSCLC with mature tertiary lymphoid structures.
查看英文原题
Spatially resolved transcriptomics reveal the determinants of primary resistance to immunotherapy in NSCLC with mature tertiary lymphoid structures.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
中文摘要
免疫检查点抑制剂（ICIs）在非小细胞肺癌（NSCLC）中的有效性已被证实与肿瘤微环境（TME）中成熟三级淋巴结构（mTLSs）的存在相关。
然而，仅有部分mTLS阳性的NSCLC患者能够从中获益，这凸显了揭示ICI应答决定因素的必要性。对来自Bergonié Institute Profiling（BIP）研究（NCT02534649）中接受ICI治疗的NSCLC患者（n = 509）进行的综合分析显示，mTLSs的存在与改善的临床结局相关，且独立于程序性死亡配体1（PD-L1）表达和基因组特征。通过空间转录组学结合多重免疫荧光（mIF），我们发现两种不同的癌症相关成纤维细胞（CAFs）亚群是介导mTLS阳性NSCLC对ICIs原发性耐药的关键因素。这些CAFs与免疫排斥、CD8+ T细胞耗竭以及调节性CD4+ T细胞浸润增加相关，提示存在免疫抑制性TME。
我们的研究强调了特定CAF亚群在阻碍ICIs中的关键作用，并提出了增强免疫治疗疗效的新治疗靶点。
展开英文摘要原文
Effectiveness of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) has been linked to the presence of mature tertiary lymphoid structures (mTLSs) within the tumor microenvironment (TME).
However, only a subset of mTLS-positive NSCLC derives benefit, thus highlighting the need to unravel ICI response determinants. The comprehensive analysis of ICI-treated patients with NSCLC (n = 509) from the Bergonié Institute Profiling (BIP) study (NCT02534649) reveals that the presence of mTLSs correlates with improved clinical outcomes, independently of programmed death ligand 1 (PD-L1) expression and genomic features.
Employing spatial transcriptomics alongside multiplex immunofluorescence (mIF), we show that two distinct subsets of cancer-associated fibroblasts (CAFs) are essential factors in mediating primary resistance to ICIs in mTLS-positive NSCLC. These CAFs are associated with immune exclusion, CD8 + T cell exhaustion, and increased regulatory CD4 + T cell infiltration, underscoring an immunosuppressive TME.
Our study highlights the pivotal role of specific CAF subsets in thwarting ICIs, proposing new therapeutic targets to enhance immunotherapy efficacy.
论文信息
- 作者
- Peyraud F、Guégan JP、Rey C、Lara O、Odin O、Del Castillo M、Vanhersecke L、Coindre JM
- 第一作者单位
- Department of Medicine, Institut Bergonié, Bordeaux, France; Faculty of Medicine, University of Bordeaux, Bordeaux, France; Explicyte Immuno-Oncology, Bordeaux, France.France
- 通讯作者单位
- Department of Medicine, Institut Bergonié, Bordeaux, France; Faculty of Medicine, University of Bordeaux, Bordeaux, France; DITEP, Gustave Roussy, Villejuif, France. Electronic address: a.italiano@bordeaux.unicancer.fr.France
- 文献类型
- 临床研究
- 期刊
- Cell reports. Medicine2025 Feb 18
- 原文标识
- PubMed 39909044 · DOI 10.1016/j.xcrm.2025.101934
在 PubMed 查看 → 出版商原文（DOI） 全文 PDF（PMC）· 可下载 治疗专题与资料阅读指南 资料来源与翻译说明 报告译文或资料问题 →