Department of Immunology, Institute of Cell Biology, University of Tübingen, 72076 Tübingen, Germany.
Immatics Biotechnologies GmbH, 72076 Tübingen, Germany.
Proc Natl Acad Sci U S A. 2017 Nov 14;114(46):E9942-E9951. doi: 10.1073/pnas.1707658114. Epub 2017 Nov 1.
Immunotherapies, particularly checkpoint inhibitors, have set off a revolution in cancer therapy by releasing the power of the immune system. However, only little is known about the antigens that are essentially presented on cancer cells, capable of exposing them to immune cells. Large-scale HLA ligandome analysis has enabled us to exhaustively characterize the immunopeptidomic landscape of epithelial ovarian cancers (EOCs). Additional comparative profiling with the immunopeptidome of a variety of benign sources has unveiled a multitude of ovarian cancer antigens (MUC16, MSLN, LGALS1, IDO1, KLK10) to be presented by HLA class I and class II molecules exclusively on ovarian cancer cells. Most strikingly, ligands derived from mucin 16 and mesothelin, a molecular axis of prognostic importance in EOC, are prominent in a majority of patients. Differential gene-expression analysis has allowed us to confirm the relevance of these targets for EOC and further provided important insights into the relationship between gene transcript levels and HLA ligand presentation.
免疫疗法，特别是检查点抑制剂，通过释放免疫系统的力量，引发了癌症治疗的革命。然而，人们对基本上在癌细胞上呈现的抗原，能够将它们暴露于免疫细胞的抗原知之甚少。大规模 HLA 配体组学分析使我们能够彻底描述上皮性卵巢癌（EOC）的免疫肽组学图谱。与各种良性来源的免疫肽组学进行额外的比较分析，揭示了许多卵巢癌抗原（MUC16、MSLN、LGALS1、IDO1、KLK10）由 HLA Ⅰ类和Ⅱ类分子在上皮性卵巢癌细胞上专一地呈递。最引人注目的是，源自黏蛋白 16 和间皮素的配体，这是 EOC 中预后重要的分子轴，在大多数患者中都很突出。差异基因表达分析使我们能够确认这些靶标对 EOC 的相关性，并进一步提供了关于基因转录水平与 HLA 配体呈递之间关系的重要见解。
