Characterization of distinct immunophenotypes across pediatric brain tumor types.
Characterization of distinct immunophenotypes across pediatric brain tumor types.
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DOI：
10.4049/jimmunol.1301966
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发表时间：
2013-11-01
期刊：
影响因子：
--
通讯作者：
Foreman NK
中科院分区：
文献类型：
--
作者：
Griesinger AM;Birks DK;Donson AM;Amani V;Hoffman LM;Waziri A;Wang M;Handler MH;Foreman NK
尽管越来越多的证据表明，抗肿瘤免疫控制存在于儿科大脑中，但这些发现尚未成功应用于临床。儿童脑肿瘤免疫治疗策略发展的一个障碍是这些肿瘤微环境的免疫表型尚未确定。为了解决这一问题，本研究使用多色流式细胞仪对肿瘤进行分类，以系统地表征在最常见的儿童脑肿瘤类型中浸润性免疫细胞的频率和表型。最初的研究队列包括7例毛细胞性星形细胞瘤(PA)、19例室管膜瘤(EPN)、5例胶质母细胞瘤(GBM)、6例髓母细胞瘤(MED)和5例非肿瘤性脑(NT)对照标本。分析的免疫细胞类型包括髓系细胞和T细胞系，以及激活或抑制的功能表型的各自标记。确定了区分每种肿瘤类型的免疫参数。PA和EPN较GBM、MED或NT有更高的髓样细胞和淋巴样细胞浸润。此外，PA和EPN表达相对活跃的/M1偏斜的髓系功能表型，特别是通过表达HLA-DR和CD64来表示。相反，与NT相似，GBM和MED的浸润性白细胞逐渐减少，功能表型减弱。这些发现是通过在儿童脑肿瘤的大基因表达微阵列队列中使用相应的免疫标记基因的全肿瘤表达来概括的。这种跨肿瘤比较分析的结果表明，不同的儿科脑肿瘤类型表现出不同的免疫表型，这意味着对于每种肿瘤类型，特定的免疫治疗方法可能是最有效的。
Despite increasing evidence that anti-tumor immune control exists in the pediatric brain, these findings have yet to be exploited successfully in the clinic. A barrier to development of immunotherapeutic strategies in pediatric brain tumors is that the immunophenotype of these tumors’ microenvironment has not been defined. To address this the present study used multicolor FACS of disaggregated tumor to systematically characterize the frequency and phenotype of infiltrating immune cells in the most common pediatric brain tumor types. The initial study cohort consisted of 7 pilocytic astrocytoma (PA), 19 ependymoma (EPN), 5 glioblastoma (GBM), 6 medulloblastoma (MED) and 5 non-tumor brain (NT) control samples obtained from epilepsy surgery. Immune cell types analyzed included both myeloid and T-cell lineages and respective markers of activated or suppressed functional phenotypes. Immune parameters that distinguished each of the tumor types were identified. PA and EPN demonstrated significantly higher infiltrating myeloid and lymphoid cells compared to GBM, MED or NT. Additionally, PA and EPN conveyed a comparatively activated/M1-skewed myeloid functional phenotype denoted in particular by HLA-DR and CD64 expression. In contrast, GBM and MED contained progressively fewer infiltrating leukocytes and more muted functional phenotype similar to that of NT. These findings were recapitulated using whole tumor expression of corresponding immune marker genes in a large gene expression microarray cohort of pediatric brain tumors. The results of this cross-tumor comparative analysis demonstrate that different pediatric brain tumor types exhibit distinct immunophenotypes, implying that specific immunotherapeutic approaches may be most effective for each tumor type.
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DOI：
10.1056/nejmoa1003466
发表时间：
2010-08-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hodi FS;O'Day SJ;McDermott DF;Weber RW;Sosman JA;Haanen JB;Gonzalez R;Robert C;Schadendorf D;Hassel JC;Akerley W;van den Eertwegh AJ;Lutzky J;Lorigan P;Vaubel JM;Linette GP;Hogg D;Ottensmeier CH;Lebbé C;Peschel C;Quirt I;Clark JI;Wolchok JD;Weber JS;Tian J;Yellin MJ;Nichol GM;Hoos A;Urba WJ
通讯作者：
Urba WJ
DOI：
10.1097/01.jnen.0000183345.19447.8e
发表时间：
2005-10-01
影响因子：
3.2
作者：
Huang, H;Hara, A;Ohgaki, H
通讯作者：
Ohgaki, H
影响因子：
5.8
作者：
Diederichsen, ACP;Hjelmborg, JV;Fenger, C
通讯作者：
Fenger, C
影响因子：
15.9
作者：
Birks, Diane K.;Donson, Andrew M.;Foreman, Nicholas K.
通讯作者：
Foreman, Nicholas K.
影响因子：
158.5
作者：
Kantoff, Philip W.;Higano, Celestia S.;Young, J.
通讯作者：
Young, J.