CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Stem-like exhausted and memory CD8(+) T cells in cancer.
Stem-like exhausted and memory CD8(+) T cells in cancer.
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T细胞在激活后可获得广泛的多种分化状态。在这一连续谱的两端,是配备效应机制的短寿命细胞,以及更为静息、寿命更长、具有增强增殖潜力和干细胞样发育可塑性的细胞。后者包括干细胞样耗竭T细胞和记忆T细胞,二者近年来均已成为癌症免疫和免疫治疗应答的关键决定因素。在此,我们讨论干细胞样耗竭CD8+ T细胞与记忆CD8+ T细胞在调控和功能方面的关键相似性与差异,并探讨它们在癌症不同结局中对保护性免疫的背景特异性贡献,包括肿瘤逃逸、长期控制和清除。最后,我们强调,关于干细胞样耗竭T细胞和记忆T细胞分子调控认识的最新进展,正如何被探索用于癌症免疫治疗的临床获益,例如检查点抑制、过继细胞治疗和疫苗接种。
T cells can acquire a broad spectrum of differentiation states following activation. At the extreme ends of this continuum are short-lived cells equipped with effector machinery and more quiescent, long-lived cells with heightened proliferative potential and stem cell-like developmental plasticity. The latter encompass stem-like exhausted T cells and memory T cells, both of which have recently emerged as key determinants of cancer immunity and response to immunotherapy.
Here, we discuss key similarities and differences in the regulation and function of stem-like exhausted CD8 + T cells and memory CD8 + T cells, and consider their context-specific contributions to protective immunity in diverse outcomes of cancer, including tumour escape, long-term control and eradication.
Finally, we emphasize how recent advances in the understanding of the molecular regulation of stem-like exhausted T cells and memory T cells are being explored for clinical benefit in cancer immunotherapies such as checkpoint inhibition, adoptive cell therapy and vaccination.
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