整合的单细胞和空间转录组学揭示了结直肠癌癌症的免疫景观和NKT-Th1特征
Integrated single-cell and spatial transcriptomics reveal immune landscape and NKT-Th1 signatures in colorectal cancer.
摘要(中文译文)
结直肠癌（CRC）是一种高发病率和高死亡率的常见恶性肿瘤。免疫治疗仅对部分患者获益，这凸显了探索与治疗反应相关的免疫相关特征的必要性。我们分析了来自肿瘤核心、边缘及配对正常黏膜的27,414个细胞的单细胞RNA测序数据集，以研究NKT细胞异质性。一个空间转录组学数据集表征了CRC组织中NKT细胞与Th1细胞之间的相互作用。整合来自TCGA和GEO的九个CRC队列，我们评估了NKT细胞浸润与临床结局之间的关联。鉴定NKT和Th1细胞相关基因（NTRG）并整合为NTRG评分，该评分在多个独立CRC队列中进行了系统验证，以表征其与生存和免疫治疗反应的关联。除使用多个外部转录组数据集进行多数据库验证外，我们还分析了与不同NTRG评分组相关的体细胞突变谱、GO富集和药物敏感性模式。此外，关键NTRG基因在临床CRC组织标本中使用免疫组织化学进行了生物学验证。NKT细胞浸润升高与预后改善和免疫治疗敏感性增强相关。空间分析揭示了由COLLAGEN信号介导的NKT与Th1细胞共定位。NTRG评分量化了肿瘤免疫特性，高评分与较差的总生存期但更强的免疫治疗反应相关。验证证实了正常组织与癌组织之间以及免疫治疗应答者与无应答者之间NTRG表达的差异。NTRG是一种与结直肠癌免疫景观相关的探索性多基因特征，为未来研究其与免疫治疗反应和肿瘤微环境组织的关系提供了基础。
Abstract
Colorectal cancer (CRC) is a prevalent malignancy with high morbidity and mortality. Immunotherapy benefits only a subset of patients, highlighting the need to explore immune-related signatures associated with response. We analyzed a single-cell RNA sequencing dataset of 27,414 cells from tumor core, edge, and matched normal mucosa to investigate NKT cell heterogeneity. A spatial transcriptomics dataset characterized interactions between NKT and Th1 cells in CRC tissues. Integrating nine CRC cohorts from TCGA and GEO, we assessed associations between NKT cell infiltration and clinical outcomes. NKT and Th1 cell-related genes (NTRG) were identified and integrated into an NTRG score, which was systematically validated across multiple independent CRC cohorts to characterize its associations with survival and immunotherapy response. In addition to multi-database validation using several external transcriptomic datasets, we analyzed somatic mutation profiles, GO enrichment, and drug sensitivity patterns associated with different NTRG score groups. Furthermore, key NTRG genes were biologically validated in clinical CRC tissue specimens using immunohistochemistry. Elevated NKT cell infiltration correlated with improved prognosis and enhanced immunotherapy sensitivity. Spatial analysis revealed NKT and Th1 co-localization mediated by COLLAGEN signaling. The NTRG score quantified tumor-immune properties, and high scores were linked with worse overall survival yet stronger immunotherapy response. Validation confirmed differential NTRG expression between normal and cancerous tissues and across immunotherapy responders and non-responders. NTRG is an exploratory multi-gene signature associated with the immune landscape of colorectal cancer, offering a foundation for future investigation into its relationship with immunotherapy response and tumor microenvironmental organization.
如何引用
AMA
Cunen Wu, Yuanyuan Xu, Ming Zhao, Lihuiping Tao, Dayue Darrel Duan, Jun Qian, et al. Integrated single-cell and spatial transcriptomics reveal immune landscape and NKT-Th1 signatures in colorectal cancer.. Frontiers in immunology. 2026; doi:10.3389/fimmu.2026.1774363.
APA
Cunen Wu, Yuanyuan Xu, Ming Zhao, Lihuiping Tao, Dayue Darrel Duan, Jun Qian, et al (2026). Integrated single-cell and spatial transcriptomics reveal immune landscape and NKT-Th1 signatures in colorectal cancer.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1774363
GB/T 7714
Cunen Wu, Yuanyuan Xu, Ming Zhao, Lihuiping Tao, Dayue Darrel Duan, Jun Qian, et al. Integrated single-cell and spatial transcriptomics reveal immune landscape and NKT-Th1 signatures in colorectal cancer.[J]. Frontiers in immunology, 2026 doi:10.3389/fimmu.2026.1774363.
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