title: Angiotensin converting enzyme inhibitors and angiotensin II receptor antagonist attenuate tumor growth via polarization of neutrophils toward an antitumor phenotype.
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.
authors.affiliation: Department of Pharmacology, College of Medicine, Hallym University , Chuncheon, Gangwon-do Republic of Korea.
authors.forename: Sanjeeb
authors.initials: S
authors.lastname: Shrestha
authors.affiliation: Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University , Seoul, Republic of Korea.
authors.forename: Jae Myoung
authors.initials: JM
authors.lastname: Noh
authors.affiliation: Department of Pharmacology, College of Medicine, Hallym University , Chuncheon, Gangwon-do Republic of Korea.
authors.forename: Shin-Yeong
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, College of Medicine, Hallym University , Chuncheon, Gangwon-do Republic of Korea.
authors.forename: Hwa-Yong
authors.initials: HY
authors.lastname: Ham
authors.affiliation: Department of Pharmacology, College of Medicine, Hallym University , Chuncheon, Gangwon-do Republic of Korea.
authors.forename: Yeon-Ja
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, College of Medicine, Hallym University , Chuncheon, Gangwon-do Republic of Korea.
authors.forename: Young-Jin
authors.initials: YJ
authors.lastname: Yun
authors.affiliation: Department of Anatomy and Neurobiology, College of Medicine, Hallym University , Chuncheon, Gangwon-do Republic of Korea.
authors.forename: Min-Ju
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, CHA university , Seongnam, Kyeon-ki do, Republic of Korea.
authors.forename: Min-Soo
authors.initials: MS
authors.lastname: Kwon
authors.affiliation: Department of Pharmacology, College of Medicine, Hallym University , Chuncheon, Gangwon-do Republic of Korea.
authors.forename: Dong-Keun
authors.initials: DK
authors.lastname: Song
authors.affiliation: Department of Pharmacology, College of Medicine, Hallym University , Chuncheon, Gangwon-do Republic of Korea.
authors.forename: Chang-Won
authors.initials: CW
authors.lastname: Hong
keywords: Angiotensin II; Angiotensin II type 1 receptor antagonist; Angiotensin converting enzyme inhibitor; Innate immunity; Myeloid-derived suppressor cell; neutrophil; tumor immunology