Guo Jing, Zhang Zili
Department of Gastrointestinal and Anorectal Surgery, The Third Central Hospital of Tianjin, 83 Jintang Road, Hedong District, Tianjin, 300170, China.
Sci Rep. 2025 Mar 21;15(1):9788. doi: 10.1038/s41598-025-85390-8.
Colon cancer, a prevalent malignancy, is subject to intricate immune modulation, which substantially affects both treatment efficacy and prognostic outcomes. Furthermore, colon cancer is highly heterogeneous, and our comprehensive understanding of its immune microenvironment has not yet been fully realized. There is still ample opportunity for in-depth investigation into the composition and interactions of immune cells within colon cancer, as well as their implications for disease prognosis. In this study, we employed single-cell data from colon cancer to distinguish immune cells from non-immune cells through cluster analysis. Furthermore, we conducted an in-depth analysis of myeloid and T cells, which were categorized into 20 distinct cell subpopulations. Functional enrichment analysis revealed T cells' active involvement in the Fatty Acid Metabolism and Adipogenesis pathways, while immune checkpoint-associated genes (ICGs) were notably upregulated in CD8 T cells. Subsequent analysis involved calculating gene scores to characterize cell subpopulations, which, when combined with patient survival time analysis, revealed a significant association between the gene characterization score (referred to as "imm-score") and the survival of colon cancer patients. Specifically, the presence of CD8-ANXA1-T cells was linked to shortened overall survival in the high imm-score subgroup. Subsequently, combined with genomic analysis, patients in the high imm-score subgroup exhibited elevated tumor mutation burden (TMB) and heightened activity in both the epithelial-mesenchymal transition (EMT) and Notch signaling pathway. Finally, according to our new algorithm, scores calculated predicted the effectiveness of immunotherapy for patients. The results revealed that patients with lower scores could achieve better therapeutic outcomes with immunotherapy. This study offers an extensive analysis of the interplay between T cells and myeloid cells within colon cancer tissues, exploring their impact on the survival and prognosis of colon cancer patients. Additionally, it unveils the potential significance of the imm-score in colon cancer, potentially indicating a poor prognosis and providing novel insights into the immune-regulatory mechanisms underlying the disease.
结肠癌是一种常见的恶性肿瘤,受到复杂的免疫调节,这对治疗效果和预后结果都有重大影响。此外,结肠癌具有高度异质性,我们对其免疫微环境的全面理解尚未完全实现。对结肠癌内免疫细胞的组成、相互作用及其对疾病预后的影响仍有大量深入研究的机会。在本研究中,我们利用结肠癌的单细胞数据通过聚类分析区分免疫细胞和非免疫细胞。此外,我们对髓系细胞和T细胞进行了深入分析,它们被分为20个不同的细胞亚群。功能富集分析显示T细胞积极参与脂肪酸代谢和脂肪生成途径,而免疫检查点相关基因(ICGs)在CD8 T细胞中显著上调。随后的分析涉及计算基因分数以表征细胞亚群,将其与患者生存时间分析相结合时,发现基因表征分数(称为“imm分数”)与结肠癌患者的生存之间存在显著关联。具体而言,在高imm分数亚组中,CD8-ANXA1-T细胞的存在与总生存期缩短有关。随后,结合基因组分析,高imm分数亚组的患者表现出更高的肿瘤突变负担(TMB)以及上皮-间质转化(EMT)和Notch信号通路的活性增强。最后,根据我们的新算法,计算出的分数预测了患者免疫治疗的有效性。结果显示分数较低的患者接受免疫治疗可获得更好的治疗效果。本研究对结肠癌组织内T细胞和髓系细胞之间的相互作用进行了广泛分析,探讨了它们对结肠癌患者生存和预后的影响。此外,它揭示了imm分数在结肠癌中的潜在意义,可能预示预后不良,并为该疾病潜在的免疫调节机制提供了新的见解。