title: TNF expressed by tumor-associated macrophages, but not microglia, can eliminate glioma.
abstract: It is well known that tumor necrosis factor (TNF) can have both contrary and pleiotropic effects in anti-tumor immune response. In the present study, we prepared two different tumor cell-based immunotherapy models: MCA38 adenocarcinoma and GL261 glioma intracranial interleukin-2 (IL-2)-based. Each tumor was transfected to express IL-2 with or without expression of the soluble form of tumor necrosis factor receptor type II (sTNFRII). Although mice in which TNF is blocked survive longer than IL-2 alone (35.2 versus 26 days), the reverse was observed for GL261 glioma. The differential effect on tumor growth implies enhanced TNF sensitivity of GL261 compared to MCA38. This notion is supported by the observation that TNF induces apoptosis in GL261 but not MCA38 tumors. We further examined tumor infiltrating CD11b+F4/80+ macrophages (or tumor-associated macrophages: TAM) for TNF production in vivo and found that TAM express cell surface TNF implying a role in eliminating glioma cells mediated by the cell surface form of TNF.
authors.affiliation: Department of Neurosurgery, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Jiro
authors.initials: J
authors.lastname: Nakagawa
authors.forename: Masanao
authors.initials: M
authors.lastname: Saio
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Tamakawa
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Suwa
authors.forename: Alan B
authors.initials: AB
authors.lastname: Frey
authors.forename: Kenichi
authors.initials: K
authors.lastname: Nonaka
authors.forename: Naoki
authors.initials: N
authors.lastname: Umemura
authors.forename: Hisashi
authors.initials: H
authors.lastname: Imai
authors.forename: Guan-Feng
authors.initials: GF
authors.lastname: Ouyang
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Ohe
authors.forename: Hirohito
authors.initials: H
authors.lastname: Yano
authors.forename: Sinichi
authors.initials: S
authors.lastname: Yoshimura
authors.forename: Toru
authors.initials: T
authors.lastname: Iwama
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Takami
mesh_terms: D000230:Adenocarcinoma / Q000628:therapy; D000818:Animals; D001932:Brain Neoplasms / Q000628:therapy*; D039481:CD11b Antigen / Q000032:analysis; D045744:Cell Line, Tumor; D005910:Glioma / Q000628:therapy*; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000378:metabolism; D008264:Macrophages / Q000737:chemistry / Q000276:immunology* / Q000637:transplantation*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D039481:CD11b Antigen; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha