Identification of a highly immunogenic mouse breast cancer sub cell line, 4T1-S
Identification of a highly immunogenic mouse breast cancer sub cell line, 4T1-S
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DOI：
10.1007/s13577-015-0127-1
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发表时间：
2016-04-01
期刊：
影响因子：
4.3
通讯作者：
Seino, Ken-ichiro
中科院分区：
文献类型：
--
作者：
Abe, Hirotake;Wada, Haruka;Seino, Ken-ichiro
癌症疫苗是一种有前景的临床免疫治疗策略，与传统疗法相比，有助于引发有效且特异性的抗肿瘤免疫反应。然而，肿瘤细胞免疫原性差仍然是临床应用的主要障碍，开发修饰肿瘤细胞免疫原性的新方法可能有助于改善癌症疫苗的临床效果。 4T1小鼠乳腺癌细胞系被认为是免疫原性差且转移性高的细胞系。使用该模型，我们鉴定了 4T1 的亚细胞系，命名为 4T1-Sapporo (4T1-S)，当用作针对同一细胞系的疫苗时，该亚细胞系显示出免疫原性。在接种 4T1-S 疫苗的小鼠中，皮下注射 4T1-S 导致抗肿瘤炎症反应，表现为引流淋巴结显着增大，同时伴随着活化 CD8 T 细胞和髓系细胞亚群频率的增加。此外，4T1-S疫苗不能有效诱导裸鼠肿瘤排斥，这重要表明4T1-S疫苗依赖T细胞反应来诱导肿瘤排斥。进一步分析以确定该模型中控制肿瘤免疫原性的机制可能有助于开发提高临床癌症疫苗功效的新方法。
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.