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

• Published in: Nature communications 2023-09, Vol.14 (1), p.5590-18, Article 5590
• Main Authors: Sun, Handong, Zhang, Lishen, Wang, Zhonglin, Gu, Danling, Zhu, Mengyan, Cai, Yun, Li, Lu, Tang, Jiaqi, Huang, Bin, Bosco, Bakwatanisa, Li, Ning, Wu, Lingxiang, Wu, Wei, Li, Liangyu, Liang, Yuan, Luo, Lin, Liu, Quanzhong, Zhu, Yanhui, Sun, Jie, Shi, Liang, Xia, Tiansong, Yang, Chuang, Xu, Qitong, Han, Xue, Zhang, Weiming, Liu, Jianxia, Meng, Dong, Shao, Hua, Zheng, Xiangxin, Li, Shuqin, Pan, Hua, Ke, Jing, Jiang, Wenying, Zhang, Xiaolan, Han, Xuedong, Chu, Jian, An, Hongyin, Ge, Juyan, Pan, Chi, Wang, Xiuxing, Li, Kening, Wang, Qianghu, Ding, Qiang
• Format: Article
• Language: English
• Subjects: 13/1; 13/31; 13/51; 38/39; 45/91; 631/80/304; 692/699/67/1347; Breast cancer; Cell activation; Cytotoxicity; Fatty acids; Females; Humanities and Social Sciences; Immune system; Immunology; Immunomodulation; Immunosuppression; Infiltration; Lipid peroxidation; Lipids; Lymphocytes; Lymphocytes T; Males; Malignancy; MAP kinase; Mens health; Metabolism; Metastases; Metastasis; multidisciplinary; Oxidation; Science; Science (multidisciplinary); Transcriptomes; Transcriptomics; Tumors
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-41318-2

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. Male breast cancer may involve different populations of immune cells. Here the authors use single cell transcriptomics to show that infiltration of T cells is lower in male breast cancer relative to female breast cancer, and find that this is accompanied by distinct metabolic changes.