Increased expression of the immune modulatory molecule PD-L1 (CD274) in anaplastic meningioma.
Increased expression of the immune modulatory molecule PD-L1 (CD274) in anaplastic meningioma.
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DOI：
10.18632/oncotarget.3082
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发表时间：
2015-03-10
期刊：
影响因子：
--
通讯作者：
Santagata S
中科院分区：
文献类型：
--
作者：
Du Z;Abedalthagafi M;Aizer AA;McHenry AR;Sun HH;Bray MA;Viramontes O;Machaidze R;Brastianos PK;Reardon DA;Dunn IF;Freeman GJ;Ligon KL;Carpenter AE;Alexander BM;Agar NY;Rodig SJ;Bradshaw EM;Santagata S
世卫组织III级（间变性）脑膜瘤尚无有效的药物治疗方法。这种高度恶性肿瘤患者的中位生存期不到两年。调节肿瘤微环境中抑制局部免疫反应机制的治疗方法在难治性高级别肿瘤患者中显示出显著和持久的临床反应。我们用免疫组化方法检测了291例WHO I-III级脑膜瘤的免疫浸润，用RNAscope原位杂交法检测了PD-L1 mRNA的表达，用免疫组化方法检测了PD-L1蛋白的表达。在脑膜瘤中，肿瘤浸润淋巴细胞主要是T细胞。在间变性脑膜瘤中，T细胞的数量急剧减少，包括CD4+、CD8+ T细胞和表达PD-1的细胞数量，表达免疫调节（Treg）细胞FOXP3的数量也有所增加。PD-L1在间变性脑膜瘤中的mRNA和蛋白表达均升高。使用患者来源的脑膜瘤细胞，我们证实PD-L1在脑膜瘤细胞本身中表达，而不仅仅在浸润性免疫细胞中表达。这项研究表明，高级别脑膜瘤具有免疫抑制的肿瘤微环境，Treg细胞的增加和PD-L1的升高可能有助于这些肿瘤的侵袭性表型。
There are no effective medical treatments for WHO grade III (anaplastic) meningioma. Patients with this high-grade malignancy have a median survival of less than two years. Therapeutics that modulate the mechanisms that inhibit local immune responses in the tumor microenvironment are showing significant and durable clinical responses in patients with treatment refractory high-grade tumors. We examined the immune infiltrate of 291 meningiomas including WHO grade I-III meningiomas using immunohistochemistry and we examined the expression of PD-L1 mRNA by RNAscope in situ hybridization and PD-L1 protein by immunohistochemistry. In meningioma, the tumor infiltrating lymphocytes are predominantly T cells. In anaplastic meningioma, there is a sharp decrease in the number of T cells, including the numbers of CD4+ and CD8+ T cells and cells expressing PD-1 and there is also an increase in the number of FOXP3 expressing immunoregulatory (Treg) cells. PD-L1 expression is increased in anaplastic meningioma – both mRNA and protein. Using patient derived meningioma cell, we confirm that PD-L1 is expressed in meningioma cells themselves, and not solely in infiltrating immune cells. This work indicates that high-grade meningioma harbor an immunosuppressive tumor microenviroment and that increased Treg cells and elevated PD-L1 may contribute to the aggressive phenotype of these tumors.
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影响因子：
6.4
作者：
Goutagny, Stephane;Nault, Jean C.;Kalamarides, Michel
通讯作者：
Kalamarides, Michel
DOI：
10.1038/nrc3239
发表时间：
2012-03-22
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Pardoll DM
通讯作者：
Pardoll DM
影响因子：
--
作者：
Lamszus, K;Kluwe, L;Westphal, M
通讯作者：
Westphal, M
DOI：
10.1126/science.1233009
发表时间：
2013-03-01
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Clark VE;Erson-Omay EZ;Serin A;Yin J;Cotney J;Ozduman K;Avşar T;Li J;Murray PB;Henegariu O;Yilmaz S;Günel JM;Carrión-Grant G;Yilmaz B;Grady C;Tanrikulu B;Bakircioğlu M;Kaymakçalan H;Caglayan AO;Sencar L;Ceyhun E;Atik AF;Bayri Y;Bai H;Kolb LE;Hebert RM;Omay SB;Mishra-Gorur K;Choi M;Overton JD;Holland EC;Mane S;State MW;Bilgüvar K;Baehring JM;Gutin PH;Piepmeier JM;Vortmeyer A;Brennan CW;Pamir MN;Kiliç T;Lifton RP;Noonan JP;Yasuno K;Günel M
通讯作者：
Günel M
影响因子：
--
作者：
Abedalthagafi MS;Merrill PH;Bi WL;Jones RT;Listewnik ML;Ramkissoon SH;Thorner AR;Dunn IF;Beroukhim R;Alexander BM;Brastianos PK;Francis JM;Folkerth RD;Ligon KL;Van Hummelen P;Ligon AH;Santagata S
通讯作者：
Santagata S