IL-15扩增的OT-Ⅰ细胞持续抑制小鼠黑色素瘤生长(英文)

Tumor Repression Mediated by IL-15 Expanded CD8 T Cell Correlated With Sustained Tumor-specific CD8 T Cells in Spleen

过继免疫治疗(adoptive cell transfer,ACT)是肿瘤治疗中一种有效的免疫治疗手段,但是在没有化疗或者放疗等辅助治疗手段时,过继免疫治疗缓解肿瘤生长的效果非常短暂.为了探索一种更为有效的过继免疫治疗手段,我们使用白介素15(IL-15)体外扩增OT-ⅠCD8 T细胞,使其分化成为中央记忆性T细胞(central memory T cells,TCM),并将其过继转移至携带B16-OVA肿瘤的小鼠中.我们发现,与IL-2体外扩增的CD8 T细胞(effector T cells,TEFF)相比,TCM对肿瘤的生长具有长时间的缓解作用,而IL-2分化的TEFFs治疗肿瘤在短暂的缓解后反弹性生长.进一步的研究发现,TCM治疗的小鼠脾脏内肿瘤抗原特异性的T细胞数量和比例明显高于TEFF组,并且RT-PCR分析表明TCM治疗的小鼠肿瘤内细胞高表达MHCⅠ类分子.这些现象提示了抗原提呈对过继细胞转移治疗的效果具有重要作用.我们的研究对于发展更为有效的肿瘤免疫治疗具有提示意义.

Adoptive cell transfer （ACT） of tumor infiltrating or genetically engineered T cells is an effective immunotherapy in patients with metastatic cancer, but without additional therapies such as chemotherapy or radiotherapy, the effect was diminished and the tumor regression was also transient. To develop more effective adoptive T cell transfer therapy, central memory T cell （TCM） was expanded in vitro using IL-15 followed by transferring them into mice with B16-OVA melanoma. We found that TCM conferred a prolonged suppression of tumor growth whereas effector T cell （TEFF） cultured by IL-2 showed shorter suppression for tumor growth, which was correlated with sustained high number of tumor-specific CD8 T cells in spleen from IL-15 group. Interestingly, the expression of MHC-Ⅰ in the tumor from IL-15 group was upregulated which suggested that the cross presentation in IL-15 group was efficient. These data collectively suggested that IL-15 treated CD8 T cells elicit more effective anti-tumor response than IL-2 treated CD8 T cells owing to sustained tumor-specific CD8 T cells in spleen. Furthermore, expression of MHC-Ⅰwas upregulated in tumor in response to IL-15 mediated adoptive T cell transfer, suggesting that antigen presenting cells （APCs） were involved in adoptive T cell transfer. Our research may have implications for developing more effective tumor immunotherapy.