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胶质瘤中的免疫肿瘤微环境:聚焦于CD3 T细胞、Vδ1 T细胞和小胶质细胞/巨噬细胞。

Immune tumoral microenvironment in gliomas: focus on CD3 T cells, Vδ1 T cells, and microglia/macrophages.

作者信息

Belghali Moulay Yassine, Admou Brahim, Brahimi Maroua, Khouchani Mouna, Ba-M'hamed Saadia

机构信息

Group of Morphology and Biology of Cancers, Faculty of Medicine and Pharmacy, Cadi Ayyad University, Marrakech, Morocco.

Laboratory of Pharmacology, Neurobiology, Anthropology and Environment, Cadi Ayyad University, Marrakech, Morocco.

出版信息

Immunol Res. 2022 Apr;70(2):224-239. doi: 10.1007/s12026-022-09260-5. Epub 2022 Jan 10.

Abstract

Gliomas are histologically defined as low-grade gliomas (LGG) and high-grade gliomas (HGG). The most common type of HGG is the glioblastoma (GBM). We aimed to determine the immunological characteristics of CD3 T-cells, Vδ1 T-cells, and microglia/macrophages infiltrating brain gliomas. We collected 24 formalin-fixed paraffin-embedded samples issued from 19 cases of GBM and 5 cases of LGG. An immunohistochemical analysis was performed using anti-CD3, anti-Vδ1, and anti-iba-1 antibodies. Labelling indexes (LI) of CD3 and Vδ1 were evaluated quantitatively, and other CD3, Vδ1, and iba-1 staining characteristics were evaluated qualitatively. The median age of patients was 49 years in GBM and 52 years in LGG. The sex ratio was 1.4 and GBM predominated in males (p = 0.05). In GBM, the medians of CD3-LI and Vδ1-LI were 30 and 3.5 respectively. CD3-LI inversely correlated with survival in GBM cases (r =  - 0.543; p = 0.016). CD3 staining intensity correlated with CD3-LI (p < 0.0001) and with the survival in GBM cases (p = 0.003). Compared to LGG, the CD3-LI, the intensity of intra-tumoral Vδ1 staining, and the amount of iba-1 were higher in GBM (p = 0.042; p = 0.014; and p = 0.001 respectively). The iba-1 organization was more amoeboid in older patients and more branched in younger patients (p = 0.028) and tended to be more amoeboid in cases with high iba-1 amount (p = 0.09). Our results suggest that a high level of CD3-LI and a strong intra-tumoral infiltration of Vδ1 T-cells as well as a high involvement of TAM can be considered potential markers of poor prognosis of GBM. However, this requires further studies on more balanced GBM-LGG sample, including an expanded panel of biomarkers.

摘要

胶质瘤在组织学上分为低级别胶质瘤(LGG)和高级别胶质瘤(HGG)。最常见的HGG类型是胶质母细胞瘤(GBM)。我们旨在确定浸润脑胶质瘤的CD3 T细胞、Vδ1 T细胞和小胶质细胞/巨噬细胞的免疫特征。我们收集了19例GBM和5例LGG患者的24份福尔马林固定石蜡包埋样本。使用抗CD3、抗Vδ1和抗iba-1抗体进行免疫组织化学分析。定量评估CD3和Vδ1的标记指数(LI),定性评估其他CD3、Vδ1和iba-1染色特征。GBM患者的中位年龄为49岁,LGG患者为52岁。性别比为1.4,GBM在男性中占主导(p = 0.05)。在GBM中,CD3-LI和Vδ1-LI的中位数分别为30和3.5。GBM病例中CD3-LI与生存率呈负相关(r = -0.543;p = 0.016)。CD3染色强度与CD3-LI相关(p < 0.0001),与GBM病例的生存率相关(p = 0.003)。与LGG相比,GBM中的CD3-LI、肿瘤内Vδ1染色强度和iba-1含量更高(分别为p = 0.042;p = 0.014;p = 0.001)。iba-1的形态在老年患者中更呈阿米巴样,在年轻患者中更分支(p = 0.028),在iba-1含量高的病例中倾向于更呈阿米巴样(p = 0.09)。我们的结果表明,高水平的CD3-LI、Vδ1 T细胞在肿瘤内的强烈浸润以及肿瘤相关巨噬细胞的高度参与可被视为GBM预后不良的潜在标志物。然而,这需要对更均衡的GBM-LGG样本进行进一步研究,包括扩大生物标志物面板。

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