期刊
JAMA ONCOLOGY
卷 1, 期 9, 页码 1319-1323出版社
AMER MEDICAL ASSOC
DOI: 10.1001/jamaoncol.2015.2151
关键词
-
类别
资金
- Blavatnik Family Foundation
- National Institutes of Health/National Cancer Institute [1R01CA155010-04]
- Susan Smith Center for Women's Cancers
- Department of Defense Ovarian Cancer Academy Award [W81XWH-10-1-0585]
- Center for Immuno-Oncology at the Dana-Farber Cancer Institute
IMPORTANCE Immune checkpoint inhibitor therapy has shown benefit in various cancers, but their potential in endometrial cancer (EC) is unknown. OBSERVATIONS Prediction of neoantigen load was performed using sequencing data from the Cancer Genome Atlas data set. Evaluation of tumor-infiltrating lymphocytes (TILs) and PD-1 and PD-L1 expression was performed in 63 patients with EC referred to our institution. The predicted median (range) neoantigen load (predicted neoepitopes per sample) was proportional to the mutational load: highest in ultramutated polymerase e (POLE) tumors (8342 [628-20 440]), less in hypermutated MSI (541 [146-8063]; P <.001), and lowest in microsatellite-stable tumors (70.5 [7-1877]; P <.001). The POLE and MSI ECs exhibited higher numbers of CD3+ (44.5 vs 21.8; P =.001) and CD8+ (32.8 vs 13.5; P <.001) TILs compared with microsatellite-stable tumors. PD-1 was overexpressed in TILs (81% vs 28%; P <.001) and peritumoral lymphocytes (90% vs 28%; P <.001) of POLE and MSI tumors. PD-L1 expression was infrequently noted in tumor cells but was common in intraepithelial immune cells and more frequent in POLE and MSI tumors (39% vs 13%; P =.02). CONCLUSIONS AND RELEVANCE Polymerase e-mutated and MSI ECs are associated with high neoantigen loads and number of TILs, which is counterbalanced by overexpression of PD-1 and PD-L1. Polymerase e-mutated and MSI EC tumors may be excellent candidates for PD-1-targeted immunotherapies.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据