title: Neutrophils are Essential in Short Hairpin RNA of Indoleamine 2,3- Dioxygenase Mediated-antitumor Efficiency.
abstract: Indoleamine 2,3-dioxygenase (IDO) is a rate limiting enzyme in tryptophan-degrading pathways and IDO activity results in immune suppression. Targeting IDO is a strategy of cancer immunotherapies. Our previous studies demonstrate that delivery of short hairpin against IDO (IDO shRNA) suppresses tumor growth and increases neutrophils infiltration into tumor. Neutrophils reveal antitumorigenic "N1" or protumorigenic "N2" phenotype in tumor microenvironment. However, the function of IDO shRNA-induced neutrophils is not clear. The LLC1 lung cancer model was used to investigate the role of these neutrophils. Intramuscular injection of IDO shRNA or IDO inhibitor treatment delayed tumor growth and both treatments increased neutrophil infiltration in tumor. Enriched tumor-infiltrating neutrophils expressed both high level of tumor necrosis factor-α and tumor necrosis factor-β (N1 and N2 associated molecules, respectively). In addition, IDO shRNA treatment induced interferon-γ and tryptophan transfer RNA expression in splenocytes. Systematic depletion of neutrophils abolished the IDO shRNA-induced therapeutic effect but did not affect the effect of IDO inhibitor. The levels of interferon-γ and tumor necrosis factor-α were suppressed in IDO shRNA treatment splenocytes after neutrophils depletion. In conclusion, these tumor-infiltrating neutrophils show antitumorigenic phenotype in spleen after IDO shRNA treatment in a murine lung cancer model.
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Emergency Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.|School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Kuan-Ting
authors.initials: KT
authors.lastname: Liu
authors.affiliation: Department of Emergency Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Yao-Hua
authors.initials: YH
authors.lastname: Liu
authors.affiliation: Department of Emergency Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Hsin-Liang
authors.initials: HL
authors.lastname: Liu
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Inn-Wen
authors.initials: IW
authors.lastname: Chong
authors.affiliation: Department of Emergency Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Meng-Chi
authors.initials: MC
authors.lastname: Yen
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Institute of Medical Science and Technology, National Sun Yat-Sen University, Kaohsiung, Taiwan.
authors.forename: Po-Lin
authors.initials: PL
authors.lastname: Kuo