Integrative single-cell sequencing analysis distinguishes survival-associated cells from the breast cancer microenvironment.
Integrative single-cell sequencing analysis distinguishes survival-associated cells from the breast cancer microenvironment.
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DOI：
10.1002/cam4.5892
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发表时间：
2023-06
期刊：
影响因子：
4
通讯作者：
Chen, Liming
中科院分区：
文献类型：
--
作者：
Huang, Ling;Qin, Shijie;Xia, Lingling;Ma, Fei;Chen, Liming
乳腺癌包含多种细胞类型，显示出高度复杂的肿瘤微环境。确定肿瘤微环境中的预后细胞群将提高对乳腺癌的机制理解，并通过靶向肿瘤微环境促进乳腺癌新疗法的开发。单细胞测序的发展揭示了异质性乳腺肿瘤背景下的各种细胞类型、状态和谱系，但识别与表型相关的亚群具有挑战性。在这里，我们应用Scissor（单细胞鉴定与大样本表型相关的亚群）整合乳腺癌的单细胞和大样本数据，发现MHC缺陷的肿瘤细胞、FABP5+巨噬细胞和COL1A1+癌症相关成纤维细胞（CAFs）对患者的生存有害，而T细胞和树突状细胞是主要的保护细胞。MHC‐缺陷肿瘤细胞通过下调干扰素和JAK‐STATs信号通路，表现出强烈的MHC表达下调，从而导致免疫逃避。FABP5+巨噬细胞通过脂质代谢表现出低抗原呈递活性。我们的数据表明，COL1A1+ CAFs可能通过乳腺肿瘤微环境中的细胞相互作用阻断T细胞免疫浸润。综上所述，我们的研究揭示了乳腺癌微环境中与生存相关的亚群。重要的是，发现了与乳腺癌免疫逃避相关的亚群。整合单细胞数据和大量数据以识别预后细胞及其与乳腺癌存活相关的分子特征。
Breast cancer shows a highly complex tumor microenvironment by containing various cell types. Identifying prognostic cell populations in the tumor microenvironment will improve the mechanistical understanding of breast cancer and facilitate the development of new breast cancer therapies by targeting the tumor microenvironment. The development of single‐cell sequencing reveals various cell types, states, and lineages within the context of heterogenous breast tumors, but identifying phenotype‐associated subpopulations is challenging. Here, we applied Scissor (single‐cell identification of subpopulations with bulk Sample phenotype correlation) to integrate single cell and bulk data of breast cancer, and found that MHC‐deficient tumor cells, FABP5+ macrophages, and COL1A1+ cancer‐associated fibroblasts (CAFs) were detrimental to patient survival, while T cells and dendritic cells were the main protective cells. MHC‐deficient tumor cells show strong downregulation of MHC expression for immune evasion by downregulating interferon and JAK‐STATs signaling. FABP5+ macrophages show low antigen‐presenting activity via associating with lipid metabolism. Our data suggest that COL1A1+ CAFs may block T‐cell immune infiltration through cell interaction in breast tumor microenvironment. Taken together, our study reveals survival‐associated subpopulations in breast tumor microenvironment. Importantly, subpopulations related to immune evasion of breast cancer is uncovered. Integrating single cell data and bulk data to identify prognostic cells and their molecular characteristics related to survival of breast cancer.
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