Human effector CD8+ T cells derived from naive rather than memory subsets possess superior traits for adoptive immunotherapy
Human effector CD8+ T cells derived from naive rather than memory subsets possess superior traits for adoptive immunotherapy
复制标题
DOI：
10.1182/blood-2010-05-286286
复制
发表时间：
2011-01-20
期刊：
影响因子：
20.3
通讯作者：
Restifo, Nicholas P.
中科院分区：
文献类型：
--
作者：
Hinrichs, Christian S.;Borman, Zachary A.;Restifo, Nicholas P.
分化的簇（CD）8（+）T细胞以天真的，中心记忆和记忆子集存在，并且这些人群中的任何一个都可以在肿瘤反应性效应细胞中进行基因设计，以进行收养免疫疗法。但是，有争议的且研究了，从而导致效应子CD8（+）T细胞的最佳子集是有争议的。我们研究了人CD8（+）T细胞，发现幼稚细胞不仅是最丰富的子集，而且是最有能力体外扩张和T细胞受体转基因表达的种群。尽管膨胀增加，但天真的细胞显示出最小的效应子分化，这是一种与细胞输注后更大功效相关的质量。同样，在天真起源细胞中，在较低的水平上表达了末端分化，杀伤细胞凝集素样受体G1和CD57的标记。最后，天真衍生的效应细胞表达了较高的CD27并保留了更长的端粒，这些特征表明了更大的增殖潜力，并且与临床试验中的更大疗效有关。因此，这些数据表明，幼稚的细胞抵抗末端分化或“疲惫”，保持高复制潜力，因此可能是用于过养免疫疗法的优质子集。 （Blood.2011; 117（3）：808-814）
Cluster of differentiation (CD)8(+) T cells exist as naive, central memory, and effector memory subsets, and any of these populations can be genetically engineered in to tumor-reactive effector cells for adoptive immunotherapy. However, the optimal subset from which to derive effector CD8(+) T cells for patient treatments is controversial and understudied. We investigated human CD8(+) T cells and found that naive cells were not only the most abundant subset but also the population most capable of in vitro expansion and T-cell receptor transgene expression. Despite increased expansion, naive-derived cells displayed minimal effector differentiation, a quality associated with greater efficacy after cell infusion. Similarly, the markers of terminal differentiation, killer cell lectin-like receptor G1 and CD57, were expressed at lower levels in cells of naive origin. Finally, naive-derived effector cells expressed higher CD27 and retained longer telomeres, characteristics that suggest greater proliferative potential and that have been linked to greater efficacy in clinical trials. Thus, these data suggest that naive cells resist terminal differentiation, or "exhaustion," maintain high replicative potential, and therefore may be the superior subset for use in adoptive immunotherapy. (Blood.2011;117(3):808-814)