类似干细胞的CD8 T细胞介导了对人类癌症的采用细胞免疫疗法的反应
Sri Krishna1, Frank J Lowery1, Amy R Copeland1
1Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
概括
采用T细胞治疗 (ACT) 显示出癌症回归的前景. 研究人员确定了与成功ACT结果相关的特定瘤透淋巴细胞 (TIL) 表型,区分了干状和终端分化TIL.
科学领域:
- 免疫学
- 癌症学
- 细胞生物学
背景情况:
- 使用自身透性淋巴细胞 (TILs) 的采用性T细胞治疗 (ACT) 可以诱导癌症的完全回归.
- 与ACT临床成功相关的TIL特异型在很大程度上仍未确定.
- 了解TIL表型对于优化ACT疗效至关重要.
研究的目的:
- 研究TIL表型对TIL-ACT临床成功的影响.
- 确定与癌症完全回归和长期持久性相关的特定TIL子集.
- 描述不同TIL表型对抗瘤新抗原的功能能力.
主要方法:
- 对人类ACT产品进行高维度分析.
- 使用CD39和CD69等标记物对TIL进行表型鉴定.
- 评估TIL的持续性,自我更新和扩展能力.
- 在体内抗瘤反应的评估.
主要成果:
- 一种类似于干细胞的记忆原体表型 (CD39阴性,CD69阴性) 与完整的癌症回归和TIL持久性有关.
- 一个终端分化的表型 (CD39阳性,CD69阳性) 与较差的TIL持久性相关.
- 虽然大多数新抗原反应性TILs是终端分化的,但ACT响应者保持了一组类似茎的,新抗原特异性的TILs.
- 瘤反应型TIL表现出优异的自我更新,扩张,持久性和体内抗瘤活性.
结论:
- 调解ACT反应的TIL子集与为立即抗瘤反应而增强的不同.
- 对于ACT的持续治疗效果而言,干状的新抗原特异性TILs的存在至关重要.
- 针对这些类似茎的TIL群体进行向或丰富可能会提高ACT治疗癌症的有效性.
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