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空间分辨的C1QC⁺巨-CD4⁺ T细胞在结直肠癌微环境中的利基:对免疫疗法反应的影响

Hangyu Zhang¹, Libing Hong¹, Zhen Dong^2,3,4

¹Department of Medical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.

|July 2, 2025

概括

空间测绘显示,C1QC+巨细胞是结直肠癌免疫治疗反应的关键. 这些巨细胞与响应者中的T细胞相互作用,而非响应者中这一过程受到阻碍,提供了新的治疗点.

科学领域:

在瘤学瘤学.
免疫学免疫学免疫学
计算生物学计算生物学

背景情况:

结肠直肠癌 (CRC) 经常抵抗免疫疗法,无论微卫星不稳定性 (MSI) 或稳定性 (MSS).
空间瘤微环境 (TME) 显著影响免疫疗法结果,但仍然不完全理解.
识别空间TME特征可以区分免疫疗法响应者和不响应者.

研究的目的:

为了研究经免疫治疗的转移性CRC (mCRC) 患者的空间TME.
为详细分析细胞相互作用构建一个空间免疫图谱.
识别可预测免疫疗法反应的空间生物标志物.

主要方法:

空间多组学:成像质量细胞计,空间蛋白质组学和空间转录组学.
集成与单细胞RNA测序 (scRNA-seq) 和批量omics数据进行验证.
构建一个包含314774个细胞的空间免疫图谱.

主要成果:

在MSI和MSS亚型的免疫疗法响应者中,C1QC+寄居组织巨细胞 (RTM) 更普遍.
受访者显示C1QC+RTMs与CD4+T细胞的同位化,由MHC-II表达促进.
发现与癌症相关的纤维细胞阻碍了非响应者的这一关键免疫细胞相互作用.

结论:

空间免疫映射对于理解CRC免疫疗法反应至关重要.
C1QC+ RTM及其与T细胞的相互作用代表了预测治疗成功的潜在生物标志物.
针对空间TME,特别是巨细胞-T细胞相互作用,可能会提高CRC免疫疗法的疗效.

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The Tumor Microenvironment

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...