Angiotensin converting enzyme inhibitors and angiotensin II receptor antagonist attenuate tumor growth via polarization of neutrophils toward an antitumor phenotype. (2nd January 2016)

• Record Type: Journal Article
• Authors: Shrestha, Sanjeeb; Noh, Jae Myoung; Kim, Shin-Yeong; Ham, Hwa-Yong; Kim, Yeon-Ja; Yun, Young-Jin; Kim, Min-Ju; Kwon, Min-Soo; Song, Dong-Keun; Hong, Chang-Won
• Is Part Of: Oncoimmunology. Volume 5:Number 1(2016)
• Publication Date: 2016-01-02
• Subjects: Angiotensin converting enzyme inhibitor -- Angiotensin II type 1 receptor antagonist -- Angiotensin II -- Innate immunity -- Myeloid-derived suppressor cell -- neutrophil -- tumor immunology; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2015.1067744
• Languages: English
• ISSNs: 2162-402X

Abstract

ABSTRACT: Tumor microenvironments polarize neutrophils to protumoral phenotypes. Here, we demonstrate that the angiotensin converting enzyme inhibitors (ACEis) and angiotensin II type 1 receptor (AGTR1) antagonist attenuate tumor growth via polarization of neutrophils toward an antitumoral phenotype. The ACEis or AGTR1 antagonist enhanced hypersegmentation of human neutrophils and increased neutrophil cytotoxicity against tumor cells. This neutrophil hypersegmentation was dependent on the mTOR pathway. In a murine tumor model, ACEis and AGTR1 antagonist attenuated tumor growth and enhanced neutrophil hypersegmentation. ACEis inhibited tumor-induced polarization of neutrophils to a protumoral phenotype. Neutrophil depletion reduced the antitumor effect of ACEi. Together, these data suggest that the modulation of Ang II pathway attenuates tumor growth via polarization of neutrophils to an antitumoral phenotype.