TNF expressed by tumor-associated macrophages, but not microglia, can eliminate glioma.
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.
Nakagawa
Jiro
J
Department of Neurosurgery, Gifu University Graduate School of Medicine, Gifu, Japan.
Saio
Masanao
M
Tamakawa
Noriyuki
N
Suwa
Tatsuhiko
T
Frey
Alan B
AB
Nonaka
Kenichi
K
Umemura
Naoki
N
Imai
Hisashi
H
Ouyang
Guan-Feng
GF
Ohe
Naoyuki
N
Yano
Hirohito
H
Yoshimura
Sinichi
S
Iwama
Toru
T
Takami
Tsuyoshi
T
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*
D039481:CD11b Antigen; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha