日本名古屋大学医学研究科免疫学系Hiroyoshi Nishikawa研究组取得最新进展。他们的研究认为效应性和调节性T（Treg）T细胞之间的程序性细胞死亡蛋白1（PD-1）表达平衡可预测PD-1阻断疗法的临床疗效。该项研究成果发表在2020年8月31日的《自然-免疫学》杂志上。

他们显示肿瘤微环境中PD-1 + CD8 + T细胞相对于PD-1 + Treg细胞的频率可以预测PD-1阻断的临床疗效，并且优于其他预测因子，包括PD配体1（PD-L1）表达或肿瘤突变负荷。CD8 + T细胞和Treg细胞的PD-1表达分别对效应性和免疫抑制功能产生进行负向调控。PD-1阻滞既可导致功能障碍的PD-1 + CD8 + T细胞恢复，又可增强PD-1 + Treg细胞介导的免疫抑制作用。

通过阻断PD-1，效应性PD-1 + CD8 + T细胞而不是PD-1 + Treg细胞的彻底重新激活对于肿瘤消除是必要的。这些发现为PD-1阻断疗法提供了有望的预测性生物标志物。

据了解，免疫检查点封锁已在癌症治疗中提供了范式转变，但是这种方法的成功因素是非常可变的。因此，迫切需要可预测临床疗效的生物标志物。

附：英文原文

Title: The PD-1 expression balance between effector and regulatory T cells predicts the clinical efficacy of PD-1 blockade therapies

Author: Shogo Kumagai, Yosuke Togashi, Takahiro Kamada, Eri Sugiyama, Hitomi Nishinakamura, Yoshiko Takeuchi, Kochin Vitaly, Kota Itahashi, Yuka Maeda, Shigeyuki Matsui, Takuma Shibahara, Yasuho Yamashita, Takuma Irie, Ayaka Tsuge, Shota Fukuoka, Akihito Kawazoe, Hibiki Udagawa, Keisuke Kirita, Keiju Aokage, Genichiro Ishii, Takeshi Kuwata, Kenta Nakama, Masahito Kawazu, Toshihide Ueno, Naoya Yamazaki, Koichi Goto, Masahiro Tsuboi, Hiroyuki Mano, Toshihiko Doi, Kohei Shitara, Hiroyoshi Nishikawa

Issue&Volume: 2020-08-31

Abstract: 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 (Treg) 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 Treg 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+ Treg cell–mediated immunosuppression. A profound reactivation of effector PD-1+CD8+ T cells rather than PD-1+ Treg cells by PD-1 blockade is necessary for tumor regression. These findings provide a promising predictive biomarker for PD-1 blockade therapies.

DOI: 10.1038/s41590-020-0769-3

Source: https://www.nature.com/articles/s41590-020-0769-3