Madkouri Rachid, Kaderbhai Coureche Guillaume, Bertaut Aurélie, Truntzer Caroline, Vincent Julie, Aubriot-Lorton Marie Hélene, Farah Walid, Limagne Emeric, Ladoire Sylvain, Boidot Romain, Derangère Valentin, Ghiringhelli François
Department of Neurosurgery, CHU, Dijon, France.
Department of Medical Oncology, Georges Francois Leclerc Cancer Center, Dijon, France.
Oncoimmunology. 2017 Apr 28;6(6):e1321186. doi: 10.1080/2162402X.2017.1321186. eCollection 2017.
Interest is growing on immune cells involvement in central nervous system tumors such as glioblastoma. Even if a few reports highlighted that immune classifications could have a prognostic value, no paradigm has been clearly yet established on large and homogeneous cohorts. The aim of our study was to analyze the prognostic role of the in situ immune response of cytotoxic T cells (i.e., CD8), Foxp3 cells, Th17 and tumor-associated macrophages in glioblastoma on two independent large and homogeneous cohorts.
We worked on two large homogenous cohorts of patients having glioblastoma who underwent standard radiochemotherapy. The first cohort of 186 patients was analyzed using IHC procedures (CD8, IL-17A, FoxP3 and CD163) of surgery pieces. We next worked with transcriptomic data available online and used metagene strategy analysis for the second cohort of 525 patients.
Cytotoxic CD8 lymphocytes and Foxp3 cells were associated with a good prognosis, while Th17 were associated with a poor clinical outcome. These data were confirmed with transcriptomic analysis. Moreover, we showed for the first time a strong link between angiogenesis and Th17 metagenes expressions in glioblastoma.
Our study shows that glioblastoma bearing patients can be classified on the immune infiltrate aspects. Beyond this prognostic role of immune biomarkers, subsequent classifications could definitely help clinicians to handle targeted therapy administration and immunotherapeutic interventions.
免疫细胞参与诸如胶质母细胞瘤等中枢神经系统肿瘤的研究兴趣日益浓厚。尽管有一些报告强调免疫分类可能具有预后价值，但在大型且同质的队列中尚未明确建立起相关范式。我们研究的目的是在两个独立的大型且同质的队列中分析细胞毒性T细胞（即CD8）、Foxp3细胞、Th17和肿瘤相关巨噬细胞的原位免疫反应在胶质母细胞瘤中的预后作用。
我们研究了两个接受标准放化疗的胶质母细胞瘤患者的大型同质队列。对第一组186例患者的手术切片进行免疫组化程序（CD8、IL-17A、FoxP3和CD163）分析。接下来，我们利用在线可得的转录组数据，对第二组525例患者采用元基因策略分析。
细胞毒性CD8淋巴细胞和Foxp3细胞与良好预后相关，而Th17与不良临床结局相关。转录组分析证实了这些数据。此外，我们首次表明胶质母细胞瘤中血管生成与Th17元基因表达之间存在紧密联系。
我们的研究表明，胶质母细胞瘤患者可根据免疫浸润情况进行分类。除了免疫生物标志物的这种预后作用外，后续分类肯定有助于临床医生进行靶向治疗给药和免疫治疗干预。
