|
Hokkaido University Collection of Scholarly and Academic Papers >
Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine >
Peer-reviewed Journal Articles, etc >
Canine Transforming Growth Factor-beta Receptor 2-Ig : A Potential Candidate Biologic for Melanoma Treatment That Reverses Transforming Growth Factor-beta 1 Immunosuppression
| Title: | Canine Transforming Growth Factor-beta Receptor 2-Ig : A Potential Candidate Biologic for Melanoma Treatment That Reverses Transforming Growth Factor-beta 1 Immunosuppression |
| Authors: | Takeuchi, Hiroto Browse this author | | Konnai, Satoru Browse this author →KAKEN DB | | Maekawa, Naoya Browse this author →KAKEN DB | | Takagi, Satoshi Browse this author →KAKEN DB | | Ohta, Hiroshi Browse this author →KAKEN DB | | Sasaki, Noboru Browse this author →KAKEN DB | | Kim, Sangho Browse this author | | Okagawa, Tomohiro Browse this author →KAKEN DB | | Suzuki, Yasuhiko Browse this author →KAKEN DB | | Murata, Shiro Browse this author →KAKEN DB | | Ohashi, Kazuhiko Browse this author →KAKEN DB |
| Keywords: | canine | | melanoma | | immunosuppression | | TGF-beta 1 | | biologic | | cancer immunotherapy |
| Issue Date: | 14-Jun-2021 |
| Publisher: | Frontiers Media |
| Journal Title: | Frontiers in veterinary science |
| Volume: | 8 |
| Start Page: | 656715 |
| Publisher DOI: | 10.3389/fvets.2021.656715 |
| Abstract: | Cancer cells can evade host immune systems via multiple mechanisms. Transforming growth factor beta 1 (TGF-beta 1) is an immunosuppressive cytokine that induces regulatory T cell (Tregs) differentiation and is involved in immune evasion mechanisms in cancer. The inhibition of the TGF-beta 1 signaling pathway can suppress cancer progression and metastasis through the modulation of anticancer immune responses. However, to best of our knowledge, no implementation of treatments targeting TGF-beta 1 has been reported in dog cancers. This study aimed to examine whether TGF-beta 1 is upregulated in canine cancers. We measured TGF-beta 1 concentrations in culture supernatants of canine melanoma cell lines and in serum samples from dogs with oral malignant melanoma. TGF-beta 1 production was observed in several cell lines, and serum TGF-beta 1 levels were elevated in dogs with oral malignant melanoma. Interestingly, the addition of recombinant TGF-beta 1 to canine peripheral blood mononuclear cell cultures decreased Th1 cytokine production and increased differentiation of CD4(+)CD25(+)Foxp3(+) lymphocytes, suggesting that TGF-beta 1 is immunosuppressive in canine immune systems. We developed a decoy receptor for TGF-beta, namely TGF-beta RII-Ig, by identifying an open reading frame of the canine TGFBR2 gene. TGF-beta RII-Ig was prepared as a recombinant fusion protein of the extracellular region of canine TGF-beta RII and the Fc region of canine IgG-B. As expected, TGF-beta RII-Ig bound to TGF-beta 1. In the presence of TGF-beta 1, the treatment with TGF-beta RII-Ig increased Th1 cytokine production and decreased the differentiation of CD4(+)CD25(+)Foxp3(+) lymphocytes. Our results suggest that TGF-beta RII-Ig competitively inhibits the immunosuppressive effects of TGF-beta 1 and thereby activates immune responses. This study demonstrated the potential of TGF-beta RII-Ig as a novel biologic for canine melanoma. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/82388 |
| Appears in Collections: | 獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
|
|
