疫苗接种产生功能性原始瘤特异性CD8 T细胞和长期瘤控制
bioRxiv : the preprint server for biology
|March 11, 2024
概括
癌症疫苗,而不是免疫检查点阻塞 (ICB),通过重编程原始瘤特异性CD8 T细胞 (TST) 来阻止肝癌的进展. 这表明疫苗接种可能是早期或高风险癌症患者的最佳选择.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 癌症研究 癌症研究
背景情况:
- 免疫检查点封锁 (ICB) 在晚期癌症患者的一个子集中提供了持久的缓解.
- 癌症疫苗有望促进免疫反应,但它们对瘤免疫重编程的长期影响不太清楚.
- 用临床相关的间歇性肝癌遗传小鼠模型来研究T细胞分化和免疫疗法的有效性.
研究的目的:
- 为了比较早期与晚期肝病变中的瘤特异性CD8 T细胞 (TST) 的分化.
- 评估免疫治疗策略的有效性,包括疫苗接种和ICB,用于重编程TST并阻止肝癌的进展.
- 确定免疫能否诱导长期的瘤免疫重编程,并阻止癌症的进展.
主要方法:
- 开发了一种偶发性肝癌的遗传小鼠模型.
- 评估了SV40大T抗原 (TAG) 特定的CD8T细胞的免疫表型和功能,这些细胞在小鼠中具有早期和晚期肝损伤.
- 用弱化TAG表达Listeria monocytogenes (LMTAG),单独或与ICB一起接种疫苗的小鼠,以测试治疗干预措施.
主要成果:
- 在早期的病变中,TST是PD1+ TCF1+ TOX-并产生IFNγ. 在晚期癌症中,TST是PD1+ TCF1lo/- TOX+,缺乏效应器功能.
- 用LMTAG接种疫苗阻止了肝癌的发展,产生TCF1+ TOX-多功能细胞因子产生TST.
- 免疫检查点封锁 (ICB) 并没有减缓癌症的进展,也没有提高疫苗的疗效.
结论:
- 疫苗接种,与ICB不同,在偶发性肝癌模型中产生了原始TST并阻止了癌症的进展.
- 免疫可能是早期癌症或复发风险较高的患者最有效的策略.
- 对于成功的免疫疗法来说,响应的TST祖先群体的存在至关重要.
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