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Identification of a highly immunogenic mouse breast cancer sub cell line, 4T1-S
Authors:Hirotake Abe  Haruka Wada  Muhammad Baghdadi  Sayaka Nakanishi  Yuu Usui  Takahiro Tsuchikawa  Toshiaki Shichinohe  Satoshi Hirano  Ken-ichiro Seino
Affiliation:1.Division of Immunobiology, Institute for Genetic Medicine,Hokkaido University,Sapporo,Japan;2.Department of Gastroenterological Surgery II,Hokkaido University Graduate School of Medicine,Sapporo,Japan
Abstract:Cancer vaccines serve as a promising clinical immunotherapeutic strategy that help to trigger an effective and specific antitumor immune response compared to conventional therapies. However, poor immunogenicity of tumor cells remains a major obstacle for clinical application, and developing new methods to modify the immunogenicity of tumor cells may help to improve the clinical outcome of cancer vaccines. 4T1 mouse breast cancer cell line has been known as poorly immunogenic and highly metastatic cell line. Using this model, we identified a sub cell line of 4T1—designated as 4T1-Sapporo (4T1-S)—which shows immunogenic properties when used as a vaccine against the same line. In 4T1-S-vaccinated mice, subcutaneous injection of 4T1-S resulted in an antitumor inflammatory response represented by significant enlargement of draining lymph nodes, accompanied with increased frequencies of activated CD8 T cells and a subpopulation of myeloid cells. Additionally, 4T1-S vaccine was ineffective to induce tumor rejection in nude mice, which importantly indicate that 4T1-S vaccine rely on T cell response to induce tumor rejection. Further analysis to identify mechanisms that control tumor immunogenicity in this model may help to develop new methods for improving the efficacies of clinical cancer vaccines.
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