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脂肪酸代谢介导的男性乳腺癌转移和免疫抑制

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作者:Handong Sun #, Lishen Zhang #, Zhonglin Wang #, Danling Gu #, Mengyan Zhu, Yun Cai, Lu Li, Jiaqi Tang, Bin Huang, Bakwatanisa Bosco, Ning Li, Lingxiang Wu, Wei Wu, Liangyu Li, Yuan Liang, Lin Luo, Quanzhong Liu, Yanhui Zhu, Jie Sun, Liang Shi, Tiansong Xia, Chuang Yang, Qitong Xu, Xue Han, Weiming Z

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.

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