Samsung Genome Institute, Samsung Medical Center, Seoul 06351, Korea.
Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences &Technology, Sungkyunkwan University, Seoul 06351, Korea.
Nat Commun. 2017 May 5;8:15081. doi: 10.1038/ncomms15081.
Single-cell transcriptome profiling of tumour tissue isolates allows the characterization of heterogeneous tumour cells along with neighbouring stromal and immune cells. Here we adopt this powerful approach to breast cancer and analyse 515 cells from 11 patients. Inferred copy number variations from the single-cell RNA-seq data separate carcinoma cells from non-cancer cells. At a single-cell resolution, carcinoma cells display common signatures within the tumour as well as intratumoral heterogeneity regarding breast cancer subtype and crucial cancer-related pathways. Most of the non-cancer cells are immune cells, with three distinct clusters of T lymphocytes, B lymphocytes and macrophages. T lymphocytes and macrophages both display immunosuppressive characteristics: T cells with a regulatory or an exhausted phenotype and macrophages with an M2 phenotype. These results illustrate that the breast cancer transcriptome has a wide range of intratumoral heterogeneity, which is shaped by the tumour cells and immune cells in the surrounding microenvironment.
对肿瘤组织分离物进行单细胞转录组谱分析可以对异质性肿瘤细胞以及邻近的基质和免疫细胞进行特征描述。在这里，我们采用这种强大的方法来研究乳腺癌，并对 11 名患者的 515 个细胞进行了分析。从单细胞 RNA-seq 数据中推断出的拷贝数变异将癌性细胞与非癌性细胞区分开来。在单细胞分辨率下，癌性细胞在肿瘤内显示出共同的特征，以及乳腺癌亚型和关键癌症相关途径的肿瘤内异质性。大多数非癌性细胞是免疫细胞，其中有三个不同的 T 淋巴细胞、B 淋巴细胞和巨噬细胞簇。T 淋巴细胞和巨噬细胞都表现出免疫抑制特征：具有调节表型或耗竭表型的 T 细胞和具有 M2 表型的巨噬细胞。这些结果表明，乳腺癌转录组具有广泛的肿瘤内异质性，这种异质性是由周围微环境中的肿瘤细胞和免疫细胞塑造的。
