Department of Breast Surgery, Tongji Hospital, School of Medicine, Tongji University, Shanghai China.
College of Computer and Information Engineering, Nanjing Tech University, Nanjing, Jiangsu, China.
J Immunol. 2024 Nov 1;213(9):1392-1401. doi: 10.4049/jimmunol.2400025.
Ductal carcinoma in situ and invasive ductal carcinoma represent two stages of breast cancer progression. A multitude of studies have shown that genomic instability increases during tumor development, as manifested by higher mutation and copy number variation rates. The advent of single-cell and spatial transcriptomics has enabled the investigation of the subtle differences in cellular states during the tumor progression at single-cell level, thereby providing more nuanced understanding of the intercellular interactions within the solid tumor. However, the evolutionary trajectory of tumor cells and the establishment of the immunosuppressive microenvironment during breast cancer progression remain unclear. In this study, we performed an exploratory analysis of the single-cell sequencing dataset of 13 ductal carcinoma in situ and invasive ductal carcinoma samples. We revealed that tumor cells became more malignant and aggressive during their progression, and T cells transited to an exhausted state. The tumor cells expressed various coinhibitory ligands that interacted with the receptors of immune cells to create an immunosuppressive tumor microenvironment. Furthermore, spatial transcriptomics data confirmed the spatial colocalization of tumor and immune cells, as well as the expression of the coinhibitory ligand-receptor pairs. Our analysis provides insights into the cellular and molecular mechanism underlying the formation of the immunosuppressive landscape during two typical stages of breast cancer progression.
导管原位癌和浸润性导管癌代表乳腺癌进展的两个阶段。大量研究表明，肿瘤发展过程中基因组不稳定性增加，表现为更高的突变和拷贝数变异率。单细胞和空间转录组学的出现使得能够在单细胞水平上研究肿瘤进展过程中细胞状态的细微差异，从而更细致地了解实体瘤内细胞间的相互作用。然而，肿瘤细胞的进化轨迹和乳腺癌进展过程中免疫抑制微环境的建立仍不清楚。在这项研究中，我们对 13 个导管原位癌和浸润性导管癌样本的单细胞测序数据集进行了探索性分析。我们揭示了肿瘤细胞在进展过程中变得更加恶性和侵袭性，T 细胞过渡到衰竭状态。肿瘤细胞表达了各种共抑制配体，与免疫细胞的受体相互作用，形成免疫抑制肿瘤微环境。此外，空间转录组学数据证实了肿瘤细胞和免疫细胞的空间共定位以及共抑制配体-受体对的表达。我们的分析提供了对乳腺癌进展两个典型阶段中免疫抑制景观形成的细胞和分子机制的深入了解。
