title: Key role for neutrophils in radiation-induced antitumor immune responses: Potentiation with G-CSF.
abstract: Radiation therapy (RT), a major modality for treating localized tumors, can induce tumor regression outside the radiation field through an abscopal effect that is thought to involve the immune system. Our studies were designed to understand the early immunological effects of RT in the tumor microenvironment using several syngeneic mouse tumor models. We observed that RT induced sterile inflammation with a rapid and transient infiltration of CD11b+Gr-1high+neutrophils into the tumors. RT-recruited tumor-associated neutrophils (RT-Ns) exhibited an increased production of reactive oxygen species and induced apoptosis of tumor cells. Tumor infiltration of RT-Ns resulted in sterile inflammation and, eventually, the activation of tumor-specific cytotoxic T cells, their recruitment into the tumor site, and tumor regression. Finally, the concurrent administration of granulocyte colony-stimulating factor (G-CSF) enhanced RT-mediated antitumor activity by activating RT-Ns. Our results suggest that the combination of RT and G-CSF should be further evaluated in preclinical and clinical settings.
authors.affiliation: Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390.
authors.forename: Tsuguhide
authors.initials: T
authors.lastname: Takeshima
authors.affiliation: Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390.
authors.forename: Laurentiu M
authors.initials: LM
authors.lastname: Pop
authors.affiliation: Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390.
authors.forename: Aaron
authors.initials: A
authors.lastname: Laine
authors.affiliation: Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390.
authors.forename: Puneeth
authors.initials: P
authors.lastname: Iyengar
authors.affiliation: Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390; Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390 raquibul.hannan@utsouthwestern.edu ellen.vitetta@utsouthwestern.edu.
authors.forename: Ellen S
authors.initials: ES
authors.lastname: Vitetta
authors.affiliation: Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390; raquibul.hannan@utsouthwestern.edu ellen.vitetta@utsouthwestern.edu.
authors.forename: Raquibul
authors.initials: R
authors.lastname: Hannan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D039481:CD11b Antigen / Q000378:metabolism; D045744:Cell Line, Tumor; D018925:Chemokines / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology / Q000627:therapeutic use*; D007274:Injections, Intraperitoneal; D008198:Lymph Nodes / Q000187:drug effects / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology / Q000532:radiotherapy*; D009504:Neutrophils / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D011836:Radiation Tolerance / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects; D059016:Tumor Microenvironment / Q000187:drug effects
chemical_list: D039481:CD11b Antigen; D018925:Chemokines; D017382:Reactive Oxygen Species; D016179:Granulocyte Colony-Stimulating Factor
keywords: G-CSF; radiation therapy; tumor-associated neutrophils