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
单细胞和空间转录组分析揭示非小细胞肺癌新辅助化疗免疫治疗后的肿瘤微环境重塑
英文原题：Single-cell and spatial transcriptomic analyses revealing tumor microenvironment remodeling after neoadjuvant chemoimmunotherapy in non-small cell lung cancer.
查看英文原题
Single-cell and spatial transcriptomic analyses revealing tumor microenvironment remodeling after neoadjuvant chemoimmunotherapy in non-small cell lung cancer.
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中文摘要
非小细胞肺癌（NSCLC）是肺癌最常见的病理类型，新辅助免疫治疗联合化疗已成为NSCLC的一线治疗方案。然而，该治疗方案的疗效仍存在差异。
本研究旨在探讨化学免疫治疗对NSCLC患者的影响，以期识别与治疗敏感性潜在相关的关键分子、关键细胞亚群、通讯模式及空间分布。共收集了来自12例NSCLC患者队列的16份肺癌组织样本，并进行了单细胞RNA和空间转录组测序。
我们的数据表明，CD4 + Treg T细胞和mCAFs的分布提示免疫抑制性肿瘤微环境，而CD4 + Th17 T细胞和iCAFs的积聚可作为化学免疫治疗敏感性的阳性标志物。
此外，在阳性应答者的组织中观察到SELENOP-巨噬细胞水平显著升高，并发现SELENOP-巨噬细胞与抗原呈递癌症相关成纤维细胞（CAFs）在肿瘤边界处存在强烈的共定位，表明这两种细胞类型在联合治疗应答中具有协同作用。
此外，观察到SELENOP-巨噬细胞在三级淋巴结构中积聚，进一步提示其在募集淋巴细胞中的关键作用。此外，基于空间转录组学的细胞间通讯分析表明，在应答者中，SELENOP-巨噬细胞、apCAFs、CD4 + 和CD8 + T细胞之间的相互作用显著增强。
此外，在联合治疗应答中，SELENOP-macrophages通过胆固醇、白细胞介素、趋化因子和HLA等通路募集CD4 + Naïve、Helper和CD8 + Naïve T细胞。
本研究进一步揭示了非小细胞肺癌肿瘤微环境对联合治疗的动态空间和转录变化。
展开英文摘要原文
Non-small cell lung cancer (NSCLC) represents the most common pathological type of lung cancer, and the combination of neoadjuvant immunotherapy with chemotherapy has emerged as the first-line treatment for NSCLC. Nevertheless, the efficacy of this therapeutic approach remains variable.
The present study aims to examine the impact of chemoimmunotherapy in NSCLC patients, with a view to identifying key molecules, critical cell subpopulations, communication patterns and spatial distributions that potentially correlate with therapeutic sensitivity. A total of 16 lung cancer tissue samples were collected from a cohort of 12 NSCLC patients and subjected to single-cell RNA and spatial transcriptome sequencing.
Our data demonstrated that the distribution of CD4 + Treg T cells and mCAFs indicated an immunosuppressive tumor microenvironment, while the accumulation of CD4 + Th17 T cells and iCAFs could act as a positive marker for the sensitivity to chemoimmunotherapy.
Furthermore, a significant high level of SELENOP-macrophages was observed in tissues from positive responders, and a strong co-localization between SELENOP-macrophages and antigen-presenting cancer associated fibroblasts (CAFs) in the tumor boundaries was identified, indicating the cooperative roles of these two cell types in response to combined therapy.
Moreover, SELENOP-macrophages were observed to be accumulated in tertiary lymphoid structures, which further suggested its critical role in recruiting lymphocytes.
Furthermore, analysis of cell-cell communication, based on spatial transcriptomics, suggests that the interactions between SELENOP-macrophages, apCAFs, CD4 + and CD8 + T cells were significantly enhanced in responders.
In addition, SELENOP-macrophages recruited CD4 + Naïve, Helper and CD8 + Naïve T cells through pathways such as the cholesterol, interleukin, chemokine and HLA when responding to combined therapy. The present study further unveils the dynamic spatial and transcriptional changes in the tumor microenvironment of non-small cell lung cancer in response to combination therapy.
论文信息
- 作者
- Cui X、Liu S、Song H、Xu J、Sun Y
- 第一作者单位
- Department of Urology, First Hospital of China Medical University, Shenyang, Liaoning Province, 110001, China.China
- 通讯作者单位
- Department of Thoracic Surgery, First Hospital of China Medical University, Shenyang, Liaoning Province, 110001, China. ybsun@cmu.edu.cn.China
- 期刊
- Molecular cancer2025 Apr 9
- 原文标识
- PubMed 40205583 · DOI 10.1186/s12943-025-02287-w
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