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胶质母细胞瘤中的肿瘤浸润性T细胞亚群

Tumour-infiltrating T-cell subpopulations in glioblastomas.

作者信息

Kim Young-Hee, Jung Tae-Young, Jung Shin, Jang Woo-Youl, Moon Kyung-Sub, Kim In-Young, Lee Min-Cheol, Lee Je-Jung

机构信息

Brain Tumour Research Laboratory and Chonnam National University Research Institute of Medical Sciences, Chonnam National University Hwasun Hospital & Medical School, Gwangju, Republic of Korea.

出版信息

Br J Neurosurg. 2012 Feb;26(1):21-7. doi: 10.3109/02688697.2011.584986. Epub 2011 Jun 27.

Abstract

This study was designed to determine the incidence and prognostic value of various populations of tumour-infiltrating T cells in glioblastomas. We also evaluated the difference in T-cell populations after conventional treatment. Sixty-seven patients with glioblastomas underwent surgery between 2003 and April 2009. Immunohistochemical staining was performed for CD3, CD4, CD8 and FoxP3, and the average number and percentage of positive cells were calculated. In eight patients, the average number of subpopulations was compared between the specimens obtained during the first and second operations. Age, gender, Karnofsky performance status, Radiation Therapy Oncology Group-recursive partitioning analysis (RTOG-RPA) classes, extent of removal, treatment modality, O-6-methylguanine-DNA methyltransferase (MGMT) methylation status and immunopositivity for CD4, CD8 and FoxP3 were analyzed as prognostic factors. There was an average of 12.8 ± 1.8 CD31 T cells, 1.5 ± 0.5 CD41 T cells, 6.8 ± 1.3 CD81 T cells and 0.6 ± 0.2 FoxP3 cells. The percentage of positive T-cell subpopulations was 89.6%, 22.4%, 77.6% and 34.3% for CD3, CD4, CD8 and FoxP3, respectively. In eight patients, there was no difference in the subpopulations between the first and second operations. The median progression-free survival was 7.0 months (95% CI, 5.2-8.9 months) and the overall survival was 14.8 months (95% CI, 11-18.7 months). Univariate analysis showed a statistically significant difference in progression-free survival for CD8 (p = 0.02) and overall survival for RTOG-RPA classes (p = 0.003), the extent of removal (p = 0.01) and MGMT promoter methylation status (p = 0.005). Based on multivariate analysis, RTOG-RPA classes were significantly associated with longer overall survival. The intratumoural immune response occurred frequently in glioblastomas and there was a consistent response, even after conventional treatment. There was a statistically significant difference in progression-free survival for CD81 T cells in immunologically privileged central nervous system.

摘要

本研究旨在确定胶质母细胞瘤中各种肿瘤浸润性T细胞群体的发生率及预后价值。我们还评估了常规治疗后T细胞群体的差异。2003年至2009年4月期间,67例胶质母细胞瘤患者接受了手术。对CD3、CD4、CD8和FoxP3进行免疫组织化学染色,并计算阳性细胞的平均数和百分比。在8例患者中,比较了首次和第二次手术获取标本的亚群平均数。将年龄、性别、卡诺夫斯基功能状态、放射治疗肿瘤学组递归划分分析(RTOG-RPA)分级、切除范围、治疗方式、O-6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)甲基化状态以及CD4、CD8和FoxP3的免疫阳性作为预后因素进行分析。CD3+T细胞平均有12.8±1.8个,CD4+T细胞有1.5±0.5个,CD8+T细胞有6.8±1.3个,FoxP3细胞有0.6±0.2个。CD3、CD4、CD8和FoxP3阳性T细胞亚群的百分比分别为89.6%、22.4%、77.6%和34.3%。在8例患者中,首次和第二次手术的亚群无差异。无进展生存期的中位数为7.0个月(95%CI,5.2 - 8.9个月),总生存期为14.8个月(95%CI,11 - 18.7个月)。单因素分析显示,CD8的无进展生存期(p = 0.02)、RTOG-RPA分级的总生存期(p = 0.003)、切除范围(p = 0.01)和MGMT启动子甲基化状态(p = 0.005)存在统计学显著差异。基于多因素分析,RTOG-RPA分级与更长的总生存期显著相关。胶质母细胞瘤中肿瘤内免疫反应频繁发生,即使在常规治疗后也有一致的反应。在免疫特权的中枢神经系统中,CD8+T细胞的无进展生存期存在统计学显著差异。

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