Single-cell transcriptome analysis indicates fatty acid metabolism-mediated metastasis and immunosuppression in male breast cancer.

单细胞转录组分析表明男性乳腺癌中脂肪酸代谢介导的转移和免疫抑制。

• 影响指数: 17.694
• 发表时间: 2023 09 11
• 来源期刊: Nat Commun
• DOI: 10.1038/s41467-023-41318-2
• PMID: 37696831
• 文章类型: Journal Article
• 中科院分区: Q1
• 方向: 综合性期刊
• 作者列表: Sun H,Zhang L,Wang Z,Gu D,Zhu M,Cai Y,Li L,Tang J,Huang B,Bosco B,Li N,Wu L,Wu W,Li L,Liang Y,Luo L,Liu Q,Zhu Y,Sun J,Shi L,Xia T,Yang C,Xu Q,Han X,Zhang W,Liu J,Meng D,Shao H,Zheng X,Li S,Pan H,Ke J,Jiang W,Zhang X,Han X,Chu J,An H,Ge J,Pan C,Wang X,Li K,Wang Q,Ding Q

Mesh: Humans; Female; Male; Breast Neoplasms, Male; Single-Cell Gene Expression Analysis; Immunosuppression Therapy; Lipid Metabolism / genetics; Fatty Acids

Abstract

Male breast cancer (MBC) is a rare but aggressive malignancy with cellular and immunological characteristics that remain unclear. Here, we perform transcriptomic analysis for 111,038 single cells from tumor tissues of six MBC and thirteen female breast cancer (FBC) patients. We find that that MBC has significantly lower infiltration of T cells relative to FBC. Metastasis-related programs are more active in cancer cells from MBC. The activated fatty acid metabolism involved with FASN is related to cancer cell metastasis and low immune infiltration of MBC. T cells in MBC show activation of p38 MAPK and lipid oxidation pathways, indicating a dysfunctional state. In contrast, T cells in FBC exhibit higher expression of cytotoxic markers and immune activation pathways mediated by immune-modulatory cytokines. Moreover, we identify the inhibitory interactions between cancer cells and T cells in MBC. Our study provides important information for understanding the tumor immunology and metabolism of MBC.

摘要

男性乳腺癌（MBC）是一种罕见但侵袭性的恶性肿瘤，其细胞和免疫学特征尚不清楚。这里,我们对来自6例MBC和13例女性乳腺癌(FBC)患者肿瘤组织的111,038个单细胞进行了转录组学分析.我们发现MBC相对于FBC具有显著较低的T细胞浸润。转移相关程序在来自MBC的癌细胞中更活跃。FASN参与的活化脂肪酸代谢与癌细胞转移和MBC低免疫浸润有关。MBC中的T细胞显示p38MAPK和脂质氧化途径的激活，表明功能失调。相比之下,FBC中的T细胞表现出更高的细胞毒性标志物表达和由免疫调节细胞因子介导的免疫激活途径。此外，我们确定了MBC中癌细胞和T细胞之间的抑制性相互作用。我们的研究为了解MBC的肿瘤免疫学和代谢提供了重要信息。