Editorial
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Mar 15, 2021; 13(3): 157-160
Published online Mar 15, 2021. doi: 10.4251/wjgo.v13.i3.157
Angiotensin-converting enzyme 2 connects COVID-19 with cancer and cancer immunotherapy
Xiao-Sheng Wang
Xiao-Sheng Wang, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, Jiangsu Province, China
Author contributions: Wang XS conceived of and wrote the manuscript.
Conflict-of-interest statement: No potential conflicts of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xiao-Sheng Wang, PhD, Associate Professor, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, No. 639 Longmian Avenue, Nanjing 211198, Jiangsu Province, China. xiaosheng.wang@cpu.edu.cn
Received: December 16, 2020
Peer-review started: December 16, 2020
First decision: January 11, 2021
Revised: January 18, 2021
Accepted: February 4, 2021
Article in press: February 4, 2021
Published online: March 15, 2021
Processing time: 78 Days and 6.5 Hours
Abstract

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in more than two million deaths. Underlying diseases, including cancer, are high-risk factors for severe COVID-19 outcomes. Angiotensin-converting enzyme 2 (ACE2), as a SARS-CoV-2 host cell receptor, plays a crucial role in SARS-CoV-2 invading human cells. ACE2 also has significant associations with cancer. Recent studies showed that ACE2 was inversely correlated with the activities of multiple oncogenic pathways and tumor progression phenotypes, and was positively correlated with antitumor immune response and survival prognosis in diverse cancers, suggesting a potential protective role of ACE2 in cancer progression. Positive expression of ACE2 is also correlated with programmed death-ligand 1 (PD-L1) in cancer. The positive associations of ACE2 expression with antitumor immune signatures and PD-L1 expression indicate that ACE2 expression is a positive predictor for the response to immune checkpoint inhibitors (ICIs). This was evidenced in multiple cancer cohorts treated with ICIs. Thus, ACE2 may build potential connections between COVID-19 and cancer and cancer immunotherapy. The potential connections suggest that ACE2 inhibitors may not be a good option for treating COVID-19 patients with cancer, particularly in cancer patients who are receiving immunotherapy. Furthermore, the relationships between ACE2, COVID-19, and cancer are worth confirming by more experimental and clinical data, considering that many cancer patients are at high risk for COVID-19.

Keywords: Angiotensin-converting enzyme 2; COVID-19; Cancer progression; Antitumor immune responses; Cancer immunotherapy

Core Tip: Angiotensin-converting enzyme 2 (ACE2) is a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) host cell receptor and plays a crucial role in SARS-CoV-2 invading human cells to cause coronavirus disease 2019 (COVID-19). ACE2 also plays a role in preventing tumor progression and promoting cancer immunotherapy response. Thus, the use of ACE2 inhibitors to prevent and treat COVID-19 should be carried out cautiously in cancer patients.