2. Academic Validation
  3. Angiotensin-converting enzyme 2 identifies immuno-hot tumors suggesting angiotensin-(1-7) as a sensitizer for chemotherapy and immunotherapy in breast cancer

Angiotensin-converting enzyme 2 identifies immuno-hot tumors suggesting angiotensin-(1-7) as a sensitizer for chemotherapy and immunotherapy in breast cancer

  • Biol Proced Online. 2022 Oct 25;24(1):15. doi: 10.1186/s12575-022-00177-9.
Jie Mei # 1 2,  Yun Cai # 1 2,  Rui Xu # 3,  Xinqian Yu # 4,  Xu Han 5,  Miaomiao Weng 5,  Lingyan Chen 1,  Tao Ma 6,  Tianshu Gao 2,  Fei Gao 2,  Tiansong Xia 7,  Yichao Zhu 8,  Yan Zhang 9
Affiliations

Affiliations

  • 1 Department of Oncology, Wuxi Maternal and Child Health Hospital Affiliated to Nanjing Medical University, No. 48 Huaishu Rd, Wuxi, 214000, China.
  • 2 Wuxi Clinical Medical College, Nanjing Medical University, Wuxi, 214000, China.
  • 3 The First Clinical Medical College, Nanjing Medical University, Nanjing, 211166, China.
  • 4 Department of Physiology, Nanjing Medical University, No. 101 Longmian Av, Nanjing, 211166, China.
  • 5 Jiangsu Breast Disease Center, the First Affiliated Hospital With Nanjing Medical University, No. 300 Guangzhou Rd, Nanjing, 210029, China.
  • 6 Department of Breast Surgery, Wuxi Maternal and Child Health Hospital Affiliated to Nanjing Medical University, Wuxi, 214000, China.
  • 7 Jiangsu Breast Disease Center, the First Affiliated Hospital With Nanjing Medical University, No. 300 Guangzhou Rd, Nanjing, 210029, China. [email protected].
  • 8 Department of Physiology, Nanjing Medical University, No. 101 Longmian Av, Nanjing, 211166, China. [email protected].
  • 9 Department of Oncology, Wuxi Maternal and Child Health Hospital Affiliated to Nanjing Medical University, No. 48 Huaishu Rd, Wuxi, 214000, China. [email protected].
  • # Contributed equally.
PMID: 36284262 DOI: 10.1186/s12575-022-00177-9
Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords

ACE2; Ang-1–7; Breast cancer; Immunotherapy; Tumor microenvironment.

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