Loss of tumor suppressor PTEN function increases B7-H1 expression and immunoresistance in glioma
Loss of tumor suppressor PTEN function increases B7-H1 expression and immunoresistance in glioma
复制标题
DOI：
10.1038/nm1517
复制
发表时间：
2007-01-01
期刊：
影响因子：
82.9
通讯作者：
Pieper, Russell O.
中科院分区：
文献类型：
--
作者：
Parsa, Andrew T.;Waldron, James S.;Pieper, Russell O.
癌症免疫抵抗和免疫逃逸（1-3）可能在肿瘤进展中起重要作用，并对免疫治疗造成障碍。免疫抑制蛋白B7同源物1（B7-H1），也称为程序性死亡配体-1（PD-L1），在许多病理条件下（包括癌症）表达增加（4-10）。在这里，我们表明，在人类胶质瘤中，在磷酸酶和张力蛋白同源物（PTEN）丢失和磷脂酰肌醇-3-OH激酶（PI（3）K）通路激活后，编码B7-H1的基因表达在转录后增加。多形性胶质母细胞瘤（GBM）患者的肿瘤标本中B7-H1蛋白水平与PTEN丢失相关，肿瘤特异性T细胞比表达突变型PTEN的细胞更有效地裂解表达野生型PTEN的人胶质瘤靶细胞。这些数据确定了一种以前未被认识到的机制，该机制将肿瘤抑制因子PTEN的丧失与免疫耐受联系起来，部分由B7-H1介导。
Cancer immunoresistance and immune escape(1-3) may play important roles in tumor progression and pose obstacles for immunotherapy. Expression of the immunosuppressive protein B7 homolog 1 (B7-H1), also known as programmed death ligand-1 (PD-L1), is increased in many pathological conditions, including cancer(4-10). Here we show that expression of the gene encoding B7-H1 increases post transcriptionally in human glioma after loss of phosphatase and tensin homolog (PTEN) and activation of the phosphatidylinositol-3-OH kinase (PI(3) K) pathway. Tumor specimens from individuals with glioblastoma multiforme (GBM) had levels of B7-H1 protein that correlated with PTEN loss, and tumor-specific T cells lysed human glioma targets expressing wild-type PTEN more effectively than those expressing mutant PTEN. These data identify a previously unrecognized mechanism linking loss of the tumor suppressor PTEN with immunoresistance, mediated in part by B7-H1.