CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
肿瘤特异性 T 细胞介导的骨髓增生异常综合征细胞中 PD-L1 上调不影响 T 细胞杀伤
英文原题：Tumor-specific T cell-mediated upregulation of PD-L1 in myelodysplastic syndrome cells does not affect T-cell killing.
查看英文原题
Tumor-specific T cell-mediated upregulation of PD-L1 in myelodysplastic syndrome cells does not affect T-cell killing.
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中文摘要
PD-1:PD-L1轴是一种二元相互作用，向T细胞传递抑制信号，阻碍免疫监视和对免疫治疗的反应。在此，我们分析了一种现象：肿瘤特异性T细胞在短期培养中诱导自体MDS细胞中PD-L1上调，其机制不依赖于细胞接触，且部分依赖于IFNγ。在研究了一系列小分子抑制剂后，我们确定PD-L1上调归因于未折叠蛋白反应的PKR样ER激酶（PERK）分支。有趣的是，我们发现肿瘤特异性T细胞的细胞毒性能力并未因MDS靶细胞上PD-L1的表达而受损。这些结果突出了血液系统恶性肿瘤中PD-1:PD-L1调控的一个鲜受重视的方面，并表明这一现象虽然可能阻碍自体免疫监视，但可能不会成为诸如个性化过继性T细胞疗法等免疫治疗的障碍。
展开英文摘要原文
The PD-1:PD-L1 axis is a binary interaction that delivers inhibitory signals to T cells, impeding both immune surveillance and response to immunotherapy.
Here we analyzed a phenomenon whereby tumor-specific T cells induce PD-L1 upregulation in autologous MDS cells in short-term culture, through a mechanism that is cell-contact-independent and partially IFNγ-dependent. After investigating a panel of small-molecule inhibitors, we determined that PD-L1 upregulation was attributed to the PKR-like ER kinase (PERK) branch of the unfolded protein response.
Interestingly, we found that the cytotoxic capacity of tumor-specific T cells was not impaired by the expression of PD-L1 on MDS target cells. These results highlight a little appreciated aspect of PD-1:PD-L1 regulation in hematologic cancers and indicate that this phenomenon, while likely to hinder autochthonous immune surveillance, may not be an obstacle to immunotherapies such as personalized adoptive T-cell therapy.
论文信息
- 作者
- Ferrari V、Tarke A、Fields H、Tanaka TN、Searles S、Zanetti M
- 第一作者单位
- PersImmune, Inc., San Diego, CA, United States.United States
- 通讯作者单位
- The Laboratory of Immunology, Department of Medicine and Moores Cancer Center, University of California San Diego, La Jolla, CA, United States.United States
- 期刊
- Frontiers in oncology2022
- 原文标识
- PubMed 35992887 · DOI 10.3389/fonc.2022.915629
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