The tissue-resident marker CD103 on peripheral blood T cells predicts responses to anti-PD-1 therapy in gastric cancer
The tissue-resident marker CD103 on peripheral blood T cells predicts responses to anti-PD-1 therapy in gastric cancer
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DOI：
10.1007/s00262-022-03240-2
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发表时间：
2022-07-01
影响因子：
5.8
通讯作者：
Wada, Hisashi
中科院分区：
文献类型：
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作者：
Nose, Yohei;Saito, Takuro;Wada, Hisashi
免疫检查点抑制剂（ICI）已经彻底改变了癌症治疗。由于临床获益仅限于一部分患者，我们的目的是确定预测抗程序性细胞死亡蛋白1（PD-1）抗体（纳武单抗）在胃癌患者中疗效的外周血生物标志物。方法收集29例胃癌患者nivolumab治疗前后的外周血样本，采用流式细胞术检测nivolumab结合PD-1（+）CD8（+）T细胞表面或细胞内标志物的频率与治疗反应的关系。收集nivolumab治疗后接受胃切除术的胃癌患者的肿瘤、淋巴结和外周血，并对这些组织样本中nivolumab结合PD-1（+）CD8（+）T细胞进行表征。结果治疗开始后2周外周血PD-1（+）CD8（+）T细胞中CD103频率高的患者，其无进展生存期明显优于低频率组（P = 0.032）。CD103（+）PD-1（+）CD8（+）T细胞群主要由中央记忆T细胞组成，显示高表达Ki-67和少量细胞毒性颗粒。相反，在肿瘤中的CD 103（+）PD-1（+）CD 8（+）T细胞中更频繁地观察到效应记忆T细胞，这意味着在ICI治疗期间，淋巴结和外周血中的中央记忆T细胞向肿瘤中的效应记忆T细胞的分化状态发生了变化。结论纳武利尤单抗治疗2周后，PD-1（+）CD8（+）T细胞中CD103的高表达可能是预测抗PD-1治疗疗效的一个有用的生物标志物。
Background Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. Since clinical benefits are limited to a subset of patients, we aimed to identify peripheral blood biomarkers that predict the efficacy of the anti-programmed cell death protein 1 (PD-1) antibody (nivolumab) in patients with gastric cancer. Methods We collected peripheral blood samples from gastric cancer patients (n = 29) before and after treatment with nivolumab and investigated the relationship between the frequency of surface or intracellular markers among nivolumab-binding PD-1(+)CD8(+) T cells and treatment responses using multicolor flow cytometry. The tumors, lymph nodes, and peripheral blood of gastric cancer patients who underwent gastrectomy following nivolumab treatment were collected, and nivolumab-binding PD-1(+)CD8(+) T cells in these tissue samples were characterized. Results Patients with a high frequency of CD103 among PD-1(+)CD8(+) T cells in peripheral blood 2 weeks after the start of treatment had significantly better progression-free survival than the low group (P = 0.032). This CD103(+)PD-1(+)CD8(+) T cell population mainly consisted of central memory T cells, showing the high expression of Ki-67 and few cytotoxic granules. In contrast, effector memory T cells were more frequently observed among CD103(+)PD-1(+)CD8(+) T cells in tumors, which implied a change in the differentiated status of central memory T cells in lymph nodes and peripheral blood to effector memory T cells in tumors during the treatment with ICIs. Conclusions A high frequency of CD103 among PD-1(+)CD8(+) T cells 2 weeks after nivolumab treatment in patients with advanced gastric cancer may be a useful biomarker for predicting the efficacy of anti-PD-1 therapy.