PDF(Pubmed)
Abstract：
Radiotherapy (RT) and anti-PD-L1 synergize to enhance local and distant (abscopal) tumor control. However, clinical results in humans have been variable. With the goal of improving clinical outcomes, we investigated the underlying synergistic mechanism focusing on a CD8+ PD-1+ Tcf-1+ stem-like T cell subset in the tumor-draining lymph node (TdLN). Using murine melanoma models, we found that RT + anti-PD-L1 induces a novel differentiation program in the TdLN stem-like population which leads to their expansion and differentiation into effector cells within the tumor. Our data indicate that optimal synergy between RT + anti-PD-L1 is dependent on the TdLN stem-like T cell population as either blockade of TdLN egress or specific stem-like T cell depletion reduced tumor control. Together, these data demonstrate a multistep stimulation of stem-like T cells following combination therapy which is initiated in the TdLN and completed in the tumor.
摘要：
放射疗法(RT)和抗PD-L1协同作用以增强局部和远处(横隔)肿瘤控制。然而,人类的临床结果是可变的。为了改善临床结果，我们研究了肿瘤引流淋巴结(TdLN)中CD8+PD-1+Tcf-1+干细胞样T细胞亚群的潜在协同机制.使用小鼠黑色素瘤模型，我们发现RT+抗PD-L1在TdLN茎样细胞中诱导了一种新的分化程序,这导致它们在肿瘤内扩增并分化成效应细胞.我们的数据表明，RT+抗PD-L1之间的最佳协同作用取决于TdLN干细胞样T细胞群，因为TdLN出口的阻断或特异性干细胞样T细胞耗竭降低了肿瘤控制。一起,这些数据表明,在TdLN中开始并在肿瘤中完成的联合治疗后,干细胞样T细胞的多步骤刺激.
