血管紧张素转化酶2（ACE2）被认为是一个肿瘤抑制因子，在大多数癌症中表达低下。目前尚未深入阐明ACE2在乳腺癌（BC）中的表达模式和作用。我们进行了系统性的泛癌症分析，基于从癌症基因组图谱（TCGA）下载的RNA测序（RNA-seq）数据，评估了ACE2的表达模式和免疫学作用。评估了ACE2表达与BC肿瘤微环境（TME）中免疫特征的相关性。估计ACE2在预测治疗反应中的作用。此外，还在BALB / c小鼠BC模型中评估了ACE2产物血管紧张素-（1-7）（Ang-1-7）对化疗和免疫治疗的药效作用。此外，收集了接受新辅助化疗的BC患者的血浆样本，并将Ang-1-7表达水平与对新辅助化疗的反应进行相关分析。 与相邻组织相比，BC组织中ACE2表达低。有趣的是，ACE2在BC中与免疫调节因子、肿瘤浸润免疫细胞（TIICs）、癌症免疫循环、免疫检查点和肿瘤突变负荷（TMB）的相关性最高。此外，ACE2水平高表明对内分泌治疗反应低，而对化疗、抗- ERBB治疗、抗血管生成治疗和免疫治疗的反应高。在小鼠模型中，Ang-1-7使小鼠BC对化疗和anti-PD-1免疫治疗敏感，显示了其显著的抗肿瘤效果。此外，高水平Ang-1-7的血浆与更好的新辅助化疗反应有关。 ACE2能够识别BC中的免疫热点肿瘤，并通过重塑TME，使其酶学产物Ang-1-7对化疗和免疫治疗敏感。 ©2022年。作者（S）。

Angiotensin-converting enzyme 2 (ACE2) is known as a tumor suppressor and lowly expressed in most cancers. The expression pattern and role of ACE2 in breast cancer (BC) have not been deeply elucidated.A systematic pan-cancer analysis was conducted to assess the expression pattern and immunological role of ACE2 based on RNA-sequencing (RNA-seq) data downloaded from The Cancer Genome Atlas (TCGA). The correlation of ACE2 expression and immunological characteristics in the BC tumor microenvironment (TME) was evaluated. The role of ACE2 in predicting the response to therapeutic options was estimated. Moreover, the pharmacodynamic effect of angiotensin-(1-7) (Ang-1-7), the product of ACE2, on chemotherapy and immunotherapy was evaluated on the BALB/c mouse BC model. In addition, the plasma samples from BC patients receiving neoadjuvant chemotherapy were collected and subjected to the correlation analysis of the expression level of Ang-1-7 and the response to neoadjuvant chemotherapy.ACE2 was lowly expressed in BC tissues compared with that in adjacent tissues. Interestingly, ACE2 was shown the highest correlation with immunomodulators, tumor-infiltrating immune cells (TIICs), cancer immunity cycles, immune checkpoints, and tumor mutation burden (TMB) in BC. In addition, a high level of ACE2 indicated a low response to endocrine therapy and a high response to chemotherapy, anti-ERBB therapy, antiangiogenic therapy and immunotherapy. In the mouse model, Ang-1-7 sensitized mouse BC to the chemotherapy and anti-PD-1 immunotherapy, which revealed its significant anti-tumor effect. Moreover, a high plasma level of Ang-1-7 was associated with a better response to neoadjuvant chemotherapy.ACE2 identifies immuno-hot tumors in BC, and its enzymatic product Ang-1-7 sensitizes BC to the chemotherapy and immunotherapy by remodeling the TME.© 2022. The Author(s).