Interleukin-27 activates natural killer cells and suppresses NK-resistant head and neck squamous cell carcinoma through inducing antibody-dependent cellular cytotoxicity.
Interleukin (IL)-27 is an IL-12 family cytokine playing a pivotal role in the induction of Th1 immune responses, although its action on natural killer (NK) cells has not been fully elucidated. Here, we show that IL-27 is capable of inducing phosphorylation of signal transducers and activators of transcription 1 and 3, as well as expression of T-bet and granzyme B in murine DX-5+ NK cells. IL-27 also enhances cytotoxic activity of NK cells both in vitro and in vivo, while the in vitro viability of NK cells is also improved by this cytokine. Therapeutic administration of the IL-27 gene drastically suppressed the growth of NK-unsusceptible SCCVII tumors that had been preestablished in syngenic mice, resulting in significant prolongation of the survival of the animals. This can likely be ascribed to the antibody-dependent cellular cytotoxicity machinery because IL-27 successfully induced tumor-specific IgG in the sera of the tumor-bearing mice, and supplementation of the sera enabled IL-27-activated NK cells to kill SCCVII cells in an Fcgamma receptor III-dependent manner. These findings strongly suggest that IL-27 may offer a powerful immunotherapeutic tool to eradicate head and neck squamous cell carcinoma and other poorly immunogenic neoplasms through activating NK cells and inducing tumor-specific immunoglobulin that may cooperatively elicit antibody-dependent cellular cytotoxicity activity.
Matsui
Masahiro
M
Departments of Otorhinolaryngology-Head and Neck Surgery, and Microbiology, Kyoto Prefectural University of Medicine, Kyoto, Japan, USA.
Kishida
Tsunao
T
Nakano
Hiroshi
H
Yoshimoto
Koichiro
K
Shin-Ya
Masaharu
M
Shimada
Taketoshi
T
Nakai
Shigeru
S
Imanishi
Jiro
J
Yoshimoto
Takayuki
T
Hisa
Yasuo
Y
Mazda
Osam
O
D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D005260:Female; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D014162:Transfection
D020381:Interleukin-17