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
CCR5 表达定义了肿瘤浸润 CD8(+) T 细胞的功能异质性，并预测非小细胞肺癌中增强的抗肿瘤免疫和良好预后
英文原题：CCR5 expression defines the functional heterogeneity of tumor-infiltrating CD8(+) T cells and predicts enhanced antitumor immunity and favorable prognosis in non-small cell lung cancer.
查看英文原题
CCR5 expression defines the functional heterogeneity of tumor-infiltrating CD8(+) T cells and predicts enhanced antitumor immunity and favorable prognosis in non-small cell lung cancer.
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。
研究概要
CCR5 + CD8 + T 细胞在 NSCLC 中表现出抗肿瘤活性，可作为有前景的预后生物标志物和治疗靶点。
研究思路结论见上方概要
背景
CD8+ T细胞在抗肿瘤免疫中发挥关键作用，但其异质性导致预后关联不一致。CCR5（C-C趋化因子受体5型）是CD8+T细胞迁移进入肿瘤微环境的关键调节因子，提示CCR5+CD8+T细胞可能具有独特的抗肿瘤功能和预后意义。然而，这一假说尚未得到验证。
方法
我们通过综合分析，包括对TCGA和GEO队列的批量转录组分析、15例NSCLC患者样本的单细胞RNA测序、肿瘤组织的多重免疫荧光染色以及体外肿瘤细胞共培养杀伤实验，研究了CCR5⁺CD8⁺ T细胞在肿瘤中的作用及其在非小细胞肺癌（NSCLC）中的预后价值。
结果
我们发现，CCR5 + CD8 + T细胞高浸润水平在多个队列中与总生存期改善显著相关，并可作为独立预后因素。基因富集分析表明，CCR5上调与T细胞活化和抗肿瘤免疫增强相关。与其他CCR家族成员相比，CCR5表达与CD8 + T细胞浸润的相关性更强。功能实验显示，CCR5拮抗剂处理后肿瘤细胞裂解减少，表明T细胞细胞毒性受损。单细胞分析进一步表明，CCR5 + CD8 + T细胞代表一个功能强大的抗肿瘤亚群。
展开英文摘要原文
BACKGROUND
CD8 + T cells play a key role in antitumor immunity, but their heterogeneity leads to inconsistent prognostic associations. CCR5 (C-C chemokine receptor type 5) is a key regulator of CD8 + T cell migration into the tumor microenvironment, suggesting that CCR5 + CD8 + T cells may have unique antitumor functions and prognostic significance. However, this hypothesis has not yet been validated.
METHODS
We investigated the role of CCR5⁺CD8⁺ T cells in tumors and their prognostic value in non-small cell lung cancer (NSCLC) through comprehensive analyses including bulk transcriptomic profiling of TCGA and GEO cohorts, single-cell RNA sequencing of 15 NSCLC patient samples, multiplex immunofluorescence staining of tumor tissues, and in vitro tumor cell co-culture killing experiments.
RESULTS
We identified that high levels of CCR5 + CD8 + T cell infiltration were significantly associated with improved overall survival across multiple cohorts and served as an independent prognostic factor. Gene enrichment analysis indicated that CCR5 upregulation is linked to T cell activation and enhanced antitumor immunity. CCR5 expression correlated more strongly with CD8 + T cell infiltration than that of other CCR family members. Functional assays revealed reduced tumor cell lysis following CCR5 antagonist treatment, indicating impaired T cell cytotoxicity. Single-cell analysis further showed that CCR5 + CD8 + T cells represent a functionally potent antitumor subset.
CONCLUSION
CCR5 + CD8 + T cells exhibit antitumor activity in NSCLC and could serve as a promising prognostic biomarker and therapeutic target.
论文信息
- 作者
- Li Y、Zhang K、Wang L、Yao W、Fei W、Cheng K、Li Y、Huang G
- 第一作者单位
- Department of Oncology, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.China
- 通讯作者单位
- Department of Oncology, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China. huangguichun@seu.edu.cn.China
- 期刊
- Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico2026 Jun
- 原文标识
- PubMed 41432877 · DOI 10.1007/s12094-025-04170-y