The PD-1 expression balance between effector and regulatory T cells predicts the clinical efficacy of PD-1 blockade therapies
The PD-1 expression balance between effector and regulatory T cells predicts the clinical efficacy of PD-1 blockade therapies
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效应T细胞和调节性T细胞之间的PD-1表达平衡预测PD-1阻断疗法的临床疗效
DOI：
10.1038/s41590-020-0769-3
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发表时间：
2020-08-31
影响因子：
30.5
通讯作者：
Nishikawa, Hiroyoshi
中科院分区：
文献类型：
--
作者：
Kumagai, Shogo;Togashi, Yosuke;Nishikawa, Hiroyoshi
检查点阻断仅在一部分患者中有效;因此，可以预测疗效的生物标志物在临床上具有很高的价值。Nishkawa及其同事开发了一种基于肿瘤微环境中效应T细胞和调节T细胞PD-1阳性的生物标志物，可以准确预测检查点阻断对患者的有效性。免疫检查点阻断为癌症治疗提供了一种范式转变，但这种方法的成功是非常可变的;因此，迫切需要预测临床疗效的生物标志物。在这里，我们表明，肿瘤微环境中PD-1（+）CD8（+）T细胞相对于PD-1（+）调节性T（T-reg）细胞的频率可以预测程序性细胞死亡蛋白1（PD-1）阻断疗法的临床疗效，并且优于其他预测因素，包括PD配体1（PD-L1）表达或肿瘤突变负荷。CD8（+）T细胞和T（reg）细胞的PD-1表达分别对效应子和免疫抑制功能产生负面影响。PD-1阻断诱导功能失调的PD-1（+）CD8（+）T细胞的恢复和增强的PD-1（+）T（reg）细胞介导的免疫抑制。通过PD-1阻断效应PD-1（+）CD8（+）T细胞而不是PD-1（+）T（reg）细胞的深度再活化是肿瘤消退所必需的。这些发现为PD-1阻断疗法提供了有希望的预测生物标志物。
Checkpoint blockade is effective in only a subset of patients; therefore, biomarkers that can predict efficacy would be clinically highly valuable. Nishkawa and colleagues develop a biomarker based on PD-1 positivity of effector and regulatory T cells in the tumor microenvironment that accurately predicts the effectiveness of checkpoint blockade in patients.Immune checkpoint blockade has provided a paradigm shift in cancer therapy, but the success of this approach is very variable; therefore, biomarkers predictive of clinical efficacy are urgently required. Here, we show that the frequency of PD-1(+)CD8(+)T cells relative to that of PD-1(+)regulatory T (T-reg) cells in the tumor microenvironment can predict the clinical efficacy of programmed cell death protein 1 (PD-1) blockade therapies and is superior to other predictors, including PD ligand 1 (PD-L1) expression or tumor mutational burden. PD-1 expression by CD8(+)T cells and T(reg)cells negatively impacts effector and immunosuppressive functions, respectively. PD-1 blockade induces both recovery of dysfunctional PD-1(+)CD8(+)T cells and enhanced PD-1(+)T(reg)cell-mediated immunosuppression. A profound reactivation of effector PD-1(+)CD8(+)T cells rather than PD-1(+)T(reg)cells by PD-1 blockade is necessary for tumor regression. These findings provide a promising predictive biomarker for PD-1 blockade therapies.