CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
TIL（肿瘤浸润淋巴细胞）密度在脑膜瘤类型间的差异及其与非典型脑膜瘤预后的关联
英文原题：Tumour infiltrating lymphocyte density differs by meningioma type and is associated with prognosis in atypical meningioma.
查看英文原题
Tumour infiltrating lymphocyte density differs by meningioma type and is associated with prognosis in atypical meningioma.
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中文摘要
TIL（肿瘤浸润淋巴细胞）密度在多种肿瘤中具有预后意义，但很少有研究探讨其在脑膜瘤中的意义。本研究旨在探讨TIL密度如何因脑膜瘤组织学类型而异，以及它是否是脑膜瘤复发的预测因子。
我们使用组织微阵列和计算机辅助图像分析，研究了2002年至2011年间在奥克兰医院切除的476例脑膜瘤连续队列中CD3、CD8、CD4、FOXP3和PD-1阳性（+）TIL密度。除一例外，所有脑膜瘤中均检测到TIL（整个队列的中位CD3+ TIL密度为53.0 cells/mm 2）。大多数TIL为CD8+（中位33.6 cells/mm 2），CD4+ TIL数量较少（中位2.9 cells/mm 2）。PD-1+（中位0.32 cells/mm 2）和FOXP3+（中位0.0 cells/mm 2）TIL稀少。
与WHO I级脑膜瘤相比，WHO II/III级脑膜瘤中CD3+（p=0.0066）、CD8+（p=0.0029）和PD-1+（p=0.0375）TIL密度降低。配对比较证实，脑膜瘤类型之间TIL密度存在统计学显著差异（CD3、CD8、CD4，p<0.0001；FOXP3，p=0.0096；PD-1，p=0.0090），其中脊索样脑膜瘤的总体CD3+ TIL密度最低（中位12.5 cells/mm 2）。尽管TIL密度低，脊索样脑膜瘤的FOXP3:CD8比值高于几种脑膜瘤类型。非典型脑膜瘤的FOXP3:CD8比值高于移行型脑膜瘤（p=0.0045）。在整个队列中或按WHO分级，均未观察到TIL密度与复发之间的关联。
然而，在多变量分析中，非典型脑膜瘤中CD3+和CD8+ TIL密度与复发相关（CD3，p=0.0012；CD8，p=0.0071）。较高的CD3+和CD8+ TIL密度与改善的无复发生存期相关。
我们的研究结果表明，CD3+和CD8+ TIL密度在非典型脑膜瘤中具有预后意义。有必要对这一观察结果及其生物学基础进行进一步研究。脑膜瘤组织学类型间TIL密度的差异可能与治疗性免疫检查点抑制研究相关。
展开英文摘要原文
Tumour infiltrating lymphocyte (TIL) density is prognostically significant in various tumours, but few studies have investigated its significance in meningioma.
This study aimed to investigate how TIL density differs by meningioma histology and whether it is a predictor of meningioma recurrence.
We studied CD3, CD8, CD4, FOXP3 and PD-1 positive (+) TIL density in a continuous cohort of 476 meningiomas resected at Auckland Hospital between 2002 and 2011 using tissue microarrays and computer assisted image analysis. TILs were identified in all meningiomas except one (median CD3+ TIL density across entire cohort 53. 0 cells/mm 2 ). Most TILs were CD8+ (median 33. 6 cells/mm 2 ) with smaller numbers of CD4+ TILs (median 2. 9 cells/mm 2 ). PD-1+ (median 0. 32 cells/mm 2 ) and FOXP3+ (median 0. 0 cells/mm 2 ) TILs were scarce. Reduced CD3+ (p=0. 0066), CD8+ (p=0. 0029) and PD-1+ (p=0.
0375) TIL density was seen in WHO grade II/III meningioma compared with WHO grade I. Pairwise comparison confirmed statistically significant differences in TIL density existed between meningioma types (CD3, CD8, CD4, p<0. 0001; FOXP3, p=0. 0096; PD-1, p=0. 0090) with chordoid meningioma having the lowest overall CD3+ TIL density (median 12.
5 cells/mm 2 ). Despite its low TIL density, chordoid meningioma had a higher FOXP3:CD8 ratio than several meningioma types. Atypical meningioma had a higher FOXP3:CD8 ratio than transitional meningioma (p=0. 0045). No association between TIL density and recurrence was seen across the entire cohort or by WHO grade.
However, CD3+ and CD8+ TIL density was associated with recurrence in atypical meningioma on multivariable analysis (CD3, p=0. 0012; CD8, p=0. 0071). A higher CD3+ and CD8+ TIL density was associated with improved recurrence free survival.
Our findings suggest CD3+ and CD8+ TIL density is prognostically significant in atypical meningioma.
Further investigation of this observation and its biological basis is warranted. The differences in TIL density by meningioma histology may be of relevance in studies of therapeutic immune checkpoint inhibition.
论文信息
- 作者
- Turner CP、McLay J、Hermans IF、Correia J、Bok A、Mehrabi N、Gock S、Highet B
- 第一作者单位
- Department of Anatomical Pathology, LabPlus, Auckland City Hospital, Auckland, New Zealand; Centre for Brain Research, Department of Anatomy and Medical Imaging, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand. Electronic address: clintont@adhb.govt.nz.
- 通讯作者单位
- Centre for Brain Research, Department of Pharmacology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand. Electronic address: m.dragunow@auckland.ac.nz.
- 期刊
- Pathology2022 Jun
- 原文标识
- PubMed 35082053 · DOI 10.1016/j.pathol.2021.10.002