免疫治疗鼠获得性免疫缺陷综合征相关性淋巴瘤

Immunotherapy of murine acquired immunodeficiency syndrome-associated Bcell lymphoma

目的本研究通过T细胞输注方法阻断程序凋亡因子-1(programmed death-1,PD-1)抑制性信号在CD8+T细胞上的表达,来治疗鼠获得性免疫缺陷综合征(MAIDS)相关性B细胞淋巴瘤。方法为了选择性阻断PD-1抑制性信号通路在CD8 T细胞中的表达,采用B6.PD-1-/-小鼠作为CD8 T细胞的供体,与来自野生型B6小鼠的CD8 T细胞做比较。定期测量肿瘤直径大小,来检测PD-1-/-和野生型的CD8 T细胞抗肿瘤功能。结果我们的研究结果发现未接受CD8 T细胞输注的Rag-1-/-受体小鼠,肿瘤持续增大。接受B6.PD-1-/-CD8 T细胞输注的受体小鼠肿瘤缩小/消失的时间和速度均比接受野生型B6 CD8 T细胞输注的受体小鼠显著性缩短和加快。结论阻断CD8 T细胞中的PD-1抑制性信号通路能够增强保护性CD8 T细胞抗肿瘤的功能,可达到控制和治疗逆转录病毒感染导致MAIDS相关肿瘤的发生和发展。

This study was designed to examine whether murine acquired immunodeficiency syndrome（MAIDS）associated B-cell lymphomas could be treated with adoptive CD8 T-cell therapy by blocking the expression of inhibitory signal of programmed death-1（PD-1）. Our overall approach was to adoptively transfer PD-1-/-CD8 T cells into the tumor bearing Rag-1-/-recipient mice to selectively block the expression of PD-1 negative pathway in CD8＋T cells. And then size of the tumor was measured periodically. CD8＋T cells from wild-type B6 mice were used as control.We found that Rag-1-/-recipients, which received B6.PD-1-/-CD8 T cells, show delayed tumor growth after B6-1710 tumor challenge and eventually could clean the tumor faster than Rag-1-/-mice received equal numbers of wild-type B6.CD8 T cells, while tumors was continued to grow in Rag-1-/-recipient mice which did not receive any CD8＋T cell adoptive transfer. Our results indicate that blocking PD-1 inhibitory signaling pathway in CD8＋T cells can enhance the anti-tumor function of protective CD8＋T cells, and can be used to treat MAIDS-associated B-cell lymphomas.