Inflammation and lymphocyte infiltration are associated with shorter survival in patients with high-grade glioma
Inflammation and lymphocyte infiltration are associated with shorter survival in patients with high-grade glioma
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DOI：
10.1080/2162402x.2020.1779990
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发表时间：
2020-01-01
期刊：
影响因子：
7.2
通讯作者：
Dietrich, Pierre-Yves
中科院分区：
文献类型：
--
作者：
Marinari, Eliana;Allard, Mathilde;Dietrich, Pierre-Yves
神经胶质瘤在发病率和死亡率方面是严重的健康负担。胶质瘤中淋巴样和髓样浸润的预后意义尚不清楚。此外，肿瘤微环境中不同白细胞亚群的表征主要依赖于免疫组织化学观察，关于其与预后相关性的数据是矛盾的。在这里，我们对高级别胶质瘤患者的肿瘤浸润和循环免疫成分进行了全面的研究。通过RNA测序分析19个肿瘤活检组织和30个PBMC样品。对来自胶质瘤的癌症基因组图谱（TCGA）RNA测序数据和通过流式细胞术分析的另外39个肿瘤活检进行验证。我们确定了预后性肿瘤和外周免疫特征，这些特征将高级别胶质瘤患者的炎症增加、免疫浸润和激活与较短的总生存期相关联。重要的是，我们通过流式细胞术分析证实了我们的观察结果，并使用TCGA数据集验证了肿瘤特征。此外，肿瘤基因型和分级均与胶质瘤免疫浸润程度相关。与大多数癌症不同，胶质瘤中肿瘤部位的淋巴细胞浸润是阴性预后因素，提示免疫应答在胶质瘤中具有矛盾的促肿瘤发生作用。
Glioma represents a serious health burden in terms of morbidity and mortality. The prognostic significance of the lymphoid and myeloid infiltrates in glioma is not clearly determined. Moreover, the characterization of different leukocyte subsets in the tumor microenvironment relies mainly on immunohistochemistry observations, and data about their association with prognosis are contradictory. Here, we performed acomprehensive study of both the tumor-infiltrating and circulating immune compartments of patients with high-grade glioma. Nineteen tumor biopsies and 30 PBMC samples were analyzed by RNA sequencing. Validation was performed on The Cancer Genome Atlas (TCGA) RNA sequencing data from glioma and on additional 39 tumor biopsies analyzed by flow cytometry. We identified prognostic tumor and peripheral immune signatures, which associate increased inflammation, immune infiltration and activation with shorter overall survival in high-grade glioma patients. Importantly, we confirmed our observations by flow cytometry analysis and validated the tumor-signature using the TCGA dataset. In addition, both tumor genotype and grade associated with the degree of glioma immune infiltration. Unlike in the majority of cancers, lymphocyte infiltration at the tumor site is anegative prognostic factor in glioma, suggesting the ambivalent pro-tumorigenic role of immune responses in glioma.