研究动态
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免疫肽组学的影响:从基础研究到临床实施。

The impact of immunopeptidomics: From basic research to clinical implementation.

发表日期:2023 Feb 08
作者: Ilja E Shapiro, Michal Bassani-Sternberg
来源: SEMINARS IN IMMUNOLOGY

摘要:

免疫肽组是由人类白细胞抗原(HLA)也称为MHC分子在介导T细胞免疫监视的细胞表面呈现一组肽段。免疫肽组是细胞蛋白质组的一部分,因此它包含有关细胞健康状态的信息。肽段储备受到细胞内外扰动影响 - 如药物暴露、感染或癌变转化。免疫肽组学是一种生物分析方法,它通过高性能液相色谱与串联质谱(MS)相结合的方式从生物样品中提取呈现的肽段,并产生深度的定性和定量免疫肽组学快照。在本文中,我们对近年来发表的免疫肽组学研究进行了综述,分为三个主要领域:基础、临床前和临床研究和应用。我们回顾了关于抗原处理和呈递机制、HLA限制和推进我们对各种疾病的了解以及如何探索抗原景观已在临床前阶段实现免疫靶向的选定基础免疫肽组学研究,并为免疫肽组学的直接实施创新癌症患者治疗方案的先行探索性临床试验铺平了道路。版权所有©2023作者。由Elsevier Ltd.出版。保留所有权利。
The immunopeptidome is the set of peptides presented by the major histocompatibility complex (MHC) molecules, in humans also known as the human leukocyte antigen (HLA), on the surface of cells that mediate T-cell immunosurveillance. The immunopeptidome is a sampling of the cellular proteome and hence it contains information about the health state of cells. The peptide repertoire is influenced by intra- and extra-cellular perturbations - such as in the case of drug exposure, infection, or oncogenic transformation. Immunopeptidomics is the bioanalytical method by which the presented peptides are extracted from biological samples and analyzed by high-performance liquid chromatography coupled to tandem mass spectrometry (MS), resulting in a deep qualitative and quantitative snapshot of the immunopeptidome. In this review, we discuss published immunopeptidomics studies from recent years, grouped into three main domains: i) basic, ii) pre-clinical and iii) clinical research and applications. We review selected fundamental immunopeptidomics studies on the antigen processing and presentation machinery, on HLA restriction and studies that advanced our understanding of various diseases, and how exploration of the antigenic landscape allowed immune targeting at the pre-clinical stage, paving the way to pioneering exploratory clinical trials where immunopeptidomics is directly implemented in the conception of innovative treatments for cancer patients.Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.