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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Central memory self/tumor-reactive CD8(+) T cells confer superior antitumor immunity compared with effector memory T cells
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Central memory self/tumor-reactive CD8(+) T cells confer superior antitumor immunity compared with effector memory T cells

机译：与效应记忆T细胞相比，中央记忆自身/肿瘤反应性CD8（+）T细胞具有更高的抗肿瘤免疫力

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Central memory CD8+ T cells (T-cm) and effector memory CD8(+) T cells (T-EM) are found in humans and mice; however, their relative contributions to host immunity have only recently been examined in vivo. Further, the ability of Tcm to treat an established tumor or infection has yet to be evaluated. To address the therapeutic potential of different tumor-reactive CD8+ T cell memory subsets, we used an established model for the in vitro generation of Tcm and TEm by using IL-15 and IL-2, respectively. Adoptively transferred Tcm exhibited a potent in vivo recall response when combined with tumor-antigen vaccination and exogenous IL-2, leading to the eradication of large established tumors. By contrast, T-EM were far less effective on a per-cell basis. Microarray analysis revealed that the signature of highly in vivo effective antitumor T cells included the overexpression of genes responsible for trafficking to secondary lymphoid tissues. This gene expression profile correctly predicted the in vitro and in vivo lymphoid-homing attributes of tumor-reactive T cells. Furthermore, we found that homing to secondary lymphoid tissue is required for optimal tumor treatment. Our findings indicated that highly in vivo effective antitumor T cells were those that initially targeted secondary lymphoid tissue, rather than tumor sites, as had previously been postulated. Thus, tumor-reactive CD8(+) T cell populations with the phenotypic and functional attributes of Tcm may be superior to T-EM/effector T cells for adoptive immunotherapies using concomitant tumor-antigen vaccination.
机译：在人类和小鼠中发现了中央记忆CD8 + T细胞（T-cm）和效应记忆CD8（+）T细胞（T-EM）。然而，它们对宿主免疫的相对贡献直到最近才在体内被检查。此外，Tcm治疗已确定的肿瘤或感染的能力尚待评估。为了解决不同的肿瘤反应性CD8 + T细胞记忆亚群的治疗潜力，我们分别使用IL-15和IL-2，使用已建立的模型体外生成Tcm和TEm。当与肿瘤抗原疫苗接种和外源性IL-2结合使用时，过继转移的Tcm表现出有效的体内召回反应，从而根除了大型已建立的肿瘤。相比之下，T-EM在每个单元的基础上效果要差得多。基因芯片分析显示，高体内有效抗肿瘤T细胞的特征包括负责转运至次级淋巴组织的基因的过表达。该基因表达谱正确地预测了肿瘤反应性T细胞的体外和体内淋巴归巢特性。此外，我们发现归巢到次级淋巴组织是最佳肿瘤治疗所必需的。我们的发现表明，具有高度体内有效的抗肿瘤T细胞是那些最初靶向次级淋巴组织而不是先前假定的肿瘤部位的细胞。因此，具有Tcm的表型和功能属性的肿瘤反应性CD8（+）T细胞群体对于使用伴随的肿瘤抗原疫苗的过继免疫疗法可能优于T-EM /效应T细胞。

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