Comprehensive analysis of inhibitory checkpoint ligand expression by glioblastoma cells,Immunology and Cell Biology

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Comprehensive analysis of inhibitory checkpoint ligand expression by glioblastoma cells
Immunology and Cell Biology ( IF 3.2 ) Pub Date : 2020-11-20 , DOI: 10.1111/imcb.12428
Laverne D Robilliard _{1,

2} , Jane Yu _{1,

2} , Akshata Anchan _{1,

2} , Wayne Joseph ₃ , Graeme Finlay _{1,

3} , Catherine E Angel _{4,

5} , E Scott Graham _{1,

2}

Affiliation

Glioblastoma is a highly aggressive brain malignancy commonly refractory to classical and novel chemo‐, radio‐ and immunotherapies, with median survival times of ~15 months following diagnosis. Poor immunological responses exemplified by the downregulation of T‐cell activity, and upregulation of immunosuppressive cells within the tumor microenvironment have limited the effectiveness of immunotherapy in glioblastoma to date. Here we show that glioblastoma cells express a large repertoire of inhibitory checkpoint ligands known to control effector T cell responses. Furthermore, flow cytometry analysis reveals that glioblastoma cells with an enhanced stem cell‐like phenotype express several investigated ligands at significant levels on their cell surface. This reveals that glioblastoma stem‐like cells express suppressive ligands with the potential of suppressing major T cell checkpoint receptors. With this information, it is now essential that we understand the relevance of this extensive repertoire of immune checkpoint ligands and their functional consequence on immune evasion in glioblastoma. This is necessary to develop effective immunotherapeutics and to be able to match treatment to patient, especially in the light of CheckMate 143.

中文翻译：

胶质母细胞瘤细胞抑制性检查点配体表达的综合分析

胶质母细胞瘤是一种高度侵袭性的脑恶性肿瘤，通常对经典和新型化学、放射和免疫疗法无效，诊断后的中位生存时间约为 15 个月。迄今为止，以 T 细胞活性下调和肿瘤微环境中免疫抑制细胞上调为例的不良免疫反应限制了免疫疗法在胶质母细胞瘤中的有效性。在这里，我们展示了胶质母细胞瘤细胞表达了大量已知可控制效应 T 细胞反应的抑制性检查点配体。此外，流式细胞术分析表明，具有增强的干细胞样表型的胶质母细胞瘤细胞在其细胞表面以显着水平表达几种研究的配体。这表明胶质母细胞瘤干细胞样细胞表达具有抑制主要 T 细胞检查点受体潜力的抑制性配体。有了这些信息，我们现在必须了解这种广泛的免疫检查点配体库的相关性及其对胶质母细胞瘤免疫逃避的功能影响。这对于开发有效的免疫疗法并能够使治疗与患者相匹配是必要的，尤其是考虑到 CheckMate 143。

更新日期：2020-11-20

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