重编程瘤反应性瘤透性淋巴细胞到人类诱导的多能干细胞
S M Rafiqul Islam1,2, Takuya Maeda1,2, Naritaka Tamaoki1,2
1Surgery Branch, NCI, NIH, Bethesda, Maryland.
Cancer research communications
|June 28, 2023
概括
重新编程瘤透淋巴细胞 (TIL) 变成诱导多能干细胞 (iPSC) 会使耗尽的T细胞恢复青春. 这种方法有效地丰富了罕见的,瘤特异性T细胞受体 (TCRs),以改善采用细胞转移癌症治疗.
科学领域:
- 免疫学 免疫学 免疫学
- 干细胞生物学 干细胞生物学
- 癌症研究 癌症研究
背景情况:
- 使用瘤透淋巴细胞 (TIL) 的采用细胞转移 (ACT) 显示出治愈潜力,但受到T细胞枯竭和稀有性的限制.
- 在TIL中的瘤反应性T细胞通常表现出枯竭的表型,阻碍了它们的治疗疗效.
- 现有的方法难以从异质的TIL群体中选择性地分离和重编程瘤特异性T细胞.
研究的目的:
- 开发一种方法,将耗尽的TIL重编程为诱导多能干细胞 (iPSC),以使它们恢复青春,以加强ACT.
- 选择性地激活和丰富来自TIL的瘤反应性T细胞,以实现高效的重编程.
- 从TIL中识别和分离罕见的瘤特异性T细胞受体 (TCR).
主要方法:
- 在与自身瘤细胞共培养后,通过隔离CD8+ PD-1+ 4-1BB+ TIL来丰富瘤反应性T细胞.
- 这些丰富的TIL被直接重新编程成iPSC.
- 使用TCR测序来分析由产生的TIL-iPSC克隆编码的TCR.
主要成果:
- 在共同培养后对CD8+ PD-1+ 4-1BB+ TIL进行重编程,选择性生成瘤抗原特异性TIL-iPSCs.
- 对TIL-iPSC克隆的TCR测序揭示了与先前识别的瘤反应性TCR相同的TCR.
- 在最初的TIL群体中无法检测到的罕见瘤抗原特异性TCRs在重新编程的TIL-iPSC中被确定.
结论:
- 将TIL重新编程为iPSC可以使T细胞恢复青春,同时保留瘤特异性TCRs.
- 这种方法有效地将TIL重新编程为iPSC殖民地,其中包含各种瘤抗原反应型TCRs.
- 这种方法提供了一种独特的策略,用于从TIL中丰富和识别低频瘤抗原特异性TCR,以改善癌症免疫疗法.
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