Immune cell infiltrate differences in pilocytic astrocytoma and glioblastoma: evidence of distinct immunological microenvironments that reflect tumor biology Laboratory investigation
Immune cell infiltrate differences in pilocytic astrocytoma and glioblastoma: evidence of distinct immunological microenvironments that reflect tumor biology Laboratory investigation
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DOI：
10.3171/2011.4.jns101172
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发表时间：
2011-09-01
影响因子：
4.1
通讯作者：
Parsa, Andrew T.
中科院分区：
文献类型：
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作者：
Yang, Isaac;Han, Seunggu J.;Parsa, Andrew T.
对象。星形细胞瘤的肿瘤微环境由多种细胞类型组成，包括浸润性炎症细胞，这些细胞本质上是动态的，可能反映了肿瘤生物学。本文作者证明肿瘤内炎症浸润的特征可以区分高级别胶质母细胞瘤和低级别毛细胞星形细胞瘤。加利福尼亚大学旧金山分校对91例胶质母细胞瘤或毛细胞星形细胞瘤患者的肿瘤标本进行了分析。进行了系统的神经病理学分析。在辅助治疗前的初始手术时收集所有组织。在连续4 μ m切片上分析无坏死或出血的免疫细胞浸润。对3个不同区域（共30 x 0.237 mm(2)）连续10例hpfs进行分析。利用免疫组化技术检测浸润性细胞毒性T细胞（CD8）、自然杀伤细胞（CD56）和巨噬细胞（CD68）的标志物，对这些肿瘤中的炎症浸润进行定量分级，并根据微观解剖位置（血管周围与肿瘤内）进行分类。对照标志物包括CD3、CD20和人白细胞抗原。胶质母细胞瘤表现出明显高于毛细胞星形细胞瘤的血管周围（CD8） t细胞浸润（62% vs 29%, p = 0.0005）。血管周围（49%）和瘤内（89%,p = 0.004） cd56阳性细胞更常与胶质母细胞瘤相关。在胶质母细胞瘤中，cd68阳性细胞在血管周围和瘤内也更为普遍。在瘤内间隙，所有胶质母细胞瘤均显示cd68阳性细胞，而毛细胞星形细胞瘤为86% （p = 0.0014）。与毛细胞星形细胞瘤相比，胶质母细胞瘤中cd68阳性浸润也更为普遍（分别为97%和86%，p = 0.0003）。胶质母细胞瘤和毛细胞星形细胞瘤的cd3阳性、cd20阳性和人白细胞抗原阳性浸润无差异。该分析表明，在高级别胶质母细胞瘤和低级别毛细胞星形细胞瘤的微环境中，存在显著不同的免疫谱。这种肿瘤微环境的差异可能反映了胶质母细胞瘤肿瘤生物学的重要差异。(做!: 10.3171 / 2011.4.jns101172)
Object. The tumor microenvironment in astrocytomas is composed of a variety of cell types, including infiltrative inflammatory cells that are dynamic in nature, potentially reflecting tumor biology. In this paper the authors demonstrate that characterization of the intratumoral inflammatory infiltrate can distinguish high-grade glioblastoma from low-grade pilocytic astrocytoma.Methods. Tumor specimens from ninety-one patients with either glioblastoma or pilocytic astrocytoma were analyzed at the University of California, San Francisco. A systematic neuropathology analysis was performed. All tissue was collected at the time of the initial surgery prior to adjuvant treatment. Immune cell infiltrate not associated with necrosis or hemorrhage was analyzed on serial 4-mu m sections. Analysis was performed for 10 consecutive hpfs and in 3 separate regions (total 30 x 0.237 mm(2)). Using immunohistochemistry for markers of infiltrating cytotoxic T cells (CD8), natural killer cells (CD56), and macrophages (CD68), the inflammatory infiltrates in these tumors were graded quantitatively and classified based on microanatomical location (perivascular vs intratumoral). Control markers included CD3, CD20, and human leukocyte antigen.Results. Glioblastomas exhibited significantly higher perivascular (CD8) T-cell infiltration than pilocytic astrocytomas (62% vs 29%, p = 0.0005). Perivascular (49%) and intratumoral (89%; p = 0.004) CD56-positive cells were more commonly associated with glioblastoma. The CD68-positive cells also were more prevalent in the perivascular and intratumoral space in glioblastoma. In the intratumoral space, all glioblastomas exhibited CD68-positive cells compared with 86% of pilocytic astrocytomas (p = 0.0014). Perivascularly, CD68-positive infiltrate was also more prevalent in glioblastoma when compared with pilocytic astrocytoma (97% vs 86%, respectively; p = 0.0003). The CD3-positive, CD20-positive, and human leukocyte antigen-positive infiltrates did not differ between glioblastoma and pilocytic astrocytoma.Conclusions. This analysis suggests a significantly distinct immune profile in the microenvironment of high-grade glioblastoma versus low-grade pilocytic astrocytoma. This difference in tumor microenvironment may reflect an important difference in the tumor biology of glioblastoma. (DO!: 10.3171/2011.4.JNS101172)