微卫星不稳定性
免疫检查点
免疫疗法
医学
子宫内膜癌
封锁
黑色素瘤
肿瘤微环境
PD-L1
癌症
癌症研究
免疫系统
DNA错配修复
基因组不稳定性
疾病
肿瘤科
免疫学
内科学
基因
生物
遗传学
受体
等位基因
DNA损伤
微卫星
DNA
结直肠癌
作者
Piera Gargiulo,Chiara Della Pepa,Simona Berardi,Daniela Califano,Stefania Scala,Franco M. Buonaguro,Gennaro Ciliberto,Peter Brauchli,Sandro Pignata
标识
DOI:10.1016/j.ctrv.2016.06.008
摘要
Endometrial Cancer (EC) is still a challenge for gynecological oncologists because the treatment of the advanced disease remains an unmet need for patients. The Cancer Genome Atlas Research Network (TCGA) recently provided a comprehensive genomic and transcriptomic analysis of EC, offering a new classification of the disease, based on genetic features, which defines four subgroups of cancer rather than the two traditionally recognized. In the molecular classification two types of EC, the polymerase epsilon (POLE)-ultramutated and the microsatellite instability (MSI)-hypermutated, seem to present an enhanced immune microenvironment and a high mutation burden. The blockade of the immune checkpoints is an innovative approach that has largely demonstrated to be effective in solid malignancies, such as lung, renal and melanoma; it acts by reducing the cancer-induced immune-suppression through inhibition of the PD-1/PD-L1 (Programmed Death and PD-Ligand) axis. All available evidence supporting an over-expression of the PD-1/PD-L1 pathway in EC has been reviewed. In particular in the POLE and MSI ECs an up-regulation of this pathway was found, aiming to suggest a rationale for testing the PD-1/PD-L1 immunotherapy in these cancer subgroups.
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