Exhausted CD8+ T cells face a developmental fork in the road.
Exhausted CD8+ T cells face a developmental fork in the road.
复制标题
DOI：
10.1016/j.it.2023.02.006
复制
发表时间：
2023-03
影响因子：
16.8
通讯作者：
Ryan A Zander;W. Cui
中科院分区：
文献类型：
--
作者：
Ryan A Zander;W. Cui
在慢性病毒感染和癌症期间恢复耗尽的CD 8 +T细胞的功能是当前免疫治疗方案的主要目标。在这里，我们讨论了我们对耗尽的CD 8 +T细胞异质性的理解以及耗尽的T细胞在慢性感染和/或癌症期间遵循的潜在分化轨迹的最新进展。我们强调超越的证据表明，一些T细胞克隆是不同的性质，可以发展成终末分化的效应或耗尽的CD 8 +T细胞。最后，我们考虑了CD 8 +T细胞分化的这种分叉模型的潜在治疗意义，包括有趣的假设，即重定向祖细胞CD 8 +T细胞分化沿着效应途径可能作为一种新的方法来减轻T细胞耗竭。
Reinvigorating the function of exhausted CD8+T cells during chronic viral infection and cancer is a major goal of current immunotherapy regimens. Here, we discuss recent advances in our understanding of exhausted CD8+T cell heterogeneity as well as the potential differentiation trajectories that exhausted T cells follow during chronic infection and/or cancer. We highlight surmounting evidence suggesting that some T cell clones are divergent in nature and can develop into either terminally differentiated effector or exhausted CD8+T cells. Lastly, we consider the potential therapeutic implications of such a bifurcation model of CD8+T cell differentiation, including the intriguing hypothesis that redirecting progenitor CD8+T cell differentiation along an effector pathway may serve as a novel approach to mitigate T cell exhaustion.