Induction of systemic immunity by expression of interleukin-23 in murine colon carcinoma cells.
Interleukin-23 (IL-23), a novel cytokine composed of a newly identified p19 molecule and the p40 subunit of IL-12, can stimulate the proliferation in vitro of memory T cells. We examined whether Colon 26 murine colon carcinoma cells that were retrovirally transduced with the p19-linked p40 gene (Colon 26/IL-23) could produce antitumor effects in inoculated mice. The growth of Colon 26/IL-23 tumors developed in immunocompetent mice was significantly retarded and the tumors disappeared thereafter. Spleen cells from the mice that received Colon 26/IL-23 cells produced significant amounts of interferon-gamma, when they were cultured with irradiated Colon 26 but not irrelevant cells. Depletion of CD8(+) T cells suppressed the production of interferon-gamma. The mice that had rejected Colon 26/IL-23 tumors were resistant to subsequent challenge of parent but not irrelevant tumor cells. Colon 26/IL-23 tumors were not rejected in nude mice but the growth was retarded compared to parent tumors. Treatment of nude mice with anti-asialo GM(1) antibody did not influence the growth of Colon 26/IL-23 tumors. These data suggest that expression of IL-23 in tumors produces T cell-dependent antitumor effects and induces systemic immunity.
Wang
Yan-Qing
YQ
Division of Pathology, Chiba Cancer Center Research Institute, Chiba, Japan.
Ugai
Shin-Ichi
S
Shimozato
Osamu
O
Yu
Ling
L
Kawamura
Kiyoko
K
Yamamoto
Hiroshi
H
Yamaguchi
Taketo
T
Saisho
Hiromitsu
H
Tagawa
Masatoshi
M
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002277:Carcinoma / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D002455:Cell Division; D003110:Colonic Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D015870:Gene Expression; D015316:Genetic Therapy; D007371:Interferon-gamma / Q000096:biosynthesis; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured
C508841:Il23a protein, mouse; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins; D007371:Interferon-gamma