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Cancer Immunology, Immunotherapy
Erschienen in: Cancer Immunology, Immunotherapy 7/2008

01.07.2008 | Original Article

Interactions of host IL-6 and IFN-γ and cancer-derived TGF-β1 on MHC molecule expression during tumor spontaneous regression

verfasst von: Ya-Wen Hsiao, Kuang-Wen Liao, Tien-Fu Chung, Chen-Hsuan Liu, Chia-Da Hsu, Rea-Min Chu

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 7/2008

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Abstract

Many tumors down-regulate major histocompatibility complex (MHC) antigen expression to evade host immune surveillance. However, there are very few in vivo models to study MHC antigen expression during tumor spontaneous regression. In addition, the roles of transforming growth factor beta1 (TGF-β1), interferon gamma (IFN-γ), and interleukin (IL)-6 in modulating MHC antigen expression are ill understood. We previously reported that tumor infiltrating lymphocyte (TIL)-derived IL-6 inhibits TGF-β1 and restores natural killing (NK) activity. Using an in vivo canine-transmissible venereal tumor (CTVT) tumor model, we presently assessed IL-6 and TGF-β involvement associated with the MHC antigen expression that is commonly suppressed in cancers. IL-6, IFN-γ, and TGF-β1, closely interacted with each other and modulated MHC antigen expression. In the presence of tumor-derived TGF-β1, host IFN-γ from TIL was not active and, therefore, there was low expression of MHC antigen during tumor progression. TGF-β1-neutralizing antibody restored IFN-γ-activated MHC antigen expression on tumor cells. The addition of exogenous IL-6 that has potent anti-TGF-β1 activity restored IFN-γ activity and promoted MHC antigen expression. IFN-γ and IL-6 in combination acted synergistically to enhance the expression of MHC antigen. Thus, the three cytokines, IL-6, TGF-β1, and IFN-γ, closely interacted to modulate the MHC antigen expression. Furthermore, transcription factors, including STAT-1, STAT-3, IRF-1, NF-κB, and CREB, were significantly elevated after IL-6 and IFN-γ treatment. We conclude that the host IL-6 derived from TIL works in combination with host IFN-γ to enhance MHC molecule expression formerly inhibited by TGF-β1, driving the tumor toward regression. It is suggested that the treatment of cancer cells that constitutively secrete TGF-β1 should incorporate anti-TGF-β activity. The findings in this in vivo tumor regression model have potential applications in cancer immunotherapy.
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Metadaten
Titel
Interactions of host IL-6 and IFN-γ and cancer-derived TGF-β1 on MHC molecule expression during tumor spontaneous regression
verfasst von
Ya-Wen Hsiao
Kuang-Wen Liao
Tien-Fu Chung
Chen-Hsuan Liu
Chia-Da Hsu
Rea-Min Chu
Publikationsdatum
01.07.2008
Verlag
Springer-Verlag
Erschienen in
Cancer Immunology, Immunotherapy / Ausgabe 7/2008
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-007-0446-5

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