CD4+ and Perivascular Foxp3+ T Cells in Glioma Correlate with Angiogenesis and Tumor Progression.
CD4+ and Perivascular Foxp3+ T Cells in Glioma Correlate with Angiogenesis and Tumor Progression.
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胶质瘤中的 CD4 和血管周围 Foxp3 T 细胞与血管生成和肿瘤进展相关
DOI：
10.3389/fimmu.2017.01451
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发表时间：
2017
影响因子：
7.3
通讯作者：
Huang J
中科院分区：
文献类型：
--
作者：
Mu L;Yang C;Gao Q;Long Y;Ge H;DeLeon G;Jin L;Chang YE;Sayour EJ;Ji J;Jiang J;Kubilis PS;Qi J;Gu Y;Wang J;Song Y;Mitchell DA;Lin Z;Huang J
Angiogenesis and immune cell infiltration are key features of gliomas and their manipulation of the microenvironment, but their prognostic significance remains indeterminate. We evaluate the interconnection between tumor-infiltrating lymphocyte (TIL) and tumor blood-vasculatures in the context of glioma progression. Paired tumor tissues of 44 patients from three tumor-recurrent groups: diffuse astrocytomas (DA) recurred as DA, DA recurred as glioblastomas (GBM), and GBM recurred as GBM were evaluated by genetic analysis, immunohistochemistry for tumor blood vessel density, TIL subsets, and clinical outcomes. These cells were geographically divided into perivascular and intratumoral TILs. Associations were examined between these TILs, CD34+ tumor blood vessels, and clinical outcomes. To determine key changes in TIL subsets, microarray data of 15-paired tumors from patients who failed antiangiogenic therapy- bevacizumab, and 16-paired tumors from chemo-naïve recurrent GBM were also evaluated and compared. Upon recurrence in primary gliomas, similar kinetic changes were found between tumor blood vessels and each TIL subset in all groups, but only CD4+ including Foxp3+ TILs, positively correlated with the density of tumor blood vessels. CD4 was the predominant T cell population based on the expression of gene-transcripts in primary GBMs, and increased activated CD4+ T cells were revealed in Bevacizumab-resistant recurrent tumors (not in chemo-naïve recurrent tumors). Among these TILs, 2/3 of them were found in the perivascular niche; Foxp3+ T cells in these niches not only correlated with the tumor vessels but were also an independent predictor of shortened recurrence-free survival (RFS) (HR = 4.199, 95% CI 1.522–11.584, p = 0.006). The minimal intratumoral T cell infiltration and low detection of CD8 transcripts expression in primary GBMs can potentially limit antitumor response. CD4+ and perivascular Foxp3+ TILs associate with tumor angiogenesis and tumor progression in glioma patients. Our results suggest that combining antiangiogenic agents with immunotherapeutic approaches may help improve the antitumor efficacy for patients with malignant gliomas.
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影响因子：
11.2
作者：
Hu YL;DeLay M;Jahangiri A;Molinaro AM;Rose SD;Carbonell WS;Aghi MK
通讯作者：
Aghi MK
DOI：
10.1056/nejmoa1407279
发表时间：
2015-06-25
期刊：
The New England journal of medicine
影响因子：
--
作者：
Eckel-Passow JE;Lachance DH;Molinaro AM;Walsh KM;Decker PA;Sicotte H;Pekmezci M;Rice T;Kosel ML;Smirnov IV;Sarkar G;Caron AA;Kollmeyer TM;Praska CE;Chada AR;Halder C;Hansen HM;McCoy LS;Bracci PM;Marshall R;Zheng S;Reis GF;Pico AR;O'Neill BP;Buckner JC;Giannini C;Huse JT;Perry A;Tihan T;Berger MS;Chang SM;Prados MD;Wiemels J;Wiencke JK;Wrensch MR;Jenkins RB
通讯作者：
Jenkins RB
影响因子：
50.3
作者：
Casanovas, O;Hicklin, DJ;Hanahan, D
通讯作者：
Hanahan, D
影响因子：
1.1
作者：
Kim, Young-Hee;Jung, Tae-Young;Lee, Je-Jung
通讯作者：
Lee, Je-Jung
DOI：
10.1158/1078-0432.ccr-12-1281
发表时间：
2013-04-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Jahangiri A;De Lay M;Miller LM;Carbonell WS;Hu YL;Lu K;Tom MW;Paquette J;Tokuyasu TA;Tsao S;Marshall R;Perry A;Bjorgan KM;Chaumeil MM;Ronen SM;Bergers G;Aghi MK
通讯作者：
Aghi MK