斯坦福大学Howard Y. Chang小组宣布他们的最新研究提出了通过DNA测序大规模平行免疫肽丘提供了对癌症抗原呈递的见解。相关论文于2025年7月28日发表在《自然—遗传学》杂志上。

在这里，课题组提出ESCAPE-seq（增强单链抗原呈递测序），这是一个大规模平行平台，通过深度DNA测序全面筛选I类HLA-肽组合以供抗原呈递。ESCAPE-seq具有可编程性、高通量、敏感性和指定的病毒和癌症表位。该研究团队同时评估了超过75000种多肽-HLA组合，揭示了广泛存在的致癌驱动突变表位，以及覆盖90%人口的不同HLA-A、HLA-B和HLA-C等位基因的表位。研究组进一步鉴定了不同呈现的表位，比较了致癌热点突变和野生型。ESCAPE-seq能够一次性发现人群范围内的抗原呈递，为HLA特异性和基因组突变的免疫识别提供见解。

据了解，人类白细胞抗原（HLA）是由人类基因组中最多的多态性基因编码的。HLA I类等位基因控制T细胞识别的抗原呈递，这是自身免疫、感染性疾病和癌症的关键。目前关于HLA结合肽的知识是有限的，偏斜的，并且缺乏针对高价值靶点的人群范围的HLA结合谱。

附：英文原文

Title: Massively parallel immunopeptidome by DNA sequencing provides insights into cancer antigen presentation

Author: Shi, Quanming, Simon, Elana P., Cimen Bozkus, Cansu, Kaminska, Anna, Velazquez, Leandra, Saxena, Mansi, Zhang, Zilin, Belk, Julia A., Wang, Shuo, Yang, Nuoya, Zhang, Yaowen, Kwong, Ashley, Che, Yonglu, Stickels, Robert R., Crain, Charles R., Schmidt-Hong, Laura, Lichti, Cheryl F., Gaiha, Gaurav D., Roth, Theodore L., Bhardwaj, Nina, Satpathy, Ansuman T., Yu, Bingfei, Chang, Howard Y.

Issue&Volume: 2025-07-28

Abstract: Human leukocyte antigens (HLAs) are encoded by the most polymorphic genes in the human genome. HLA class I alleles control antigen presentation for T cell recognition, which is pivotal for autoimmunity, infectious diseases and cancer. Current knowledge of HLA-bound peptides is limited, skewed and falls short of population-wide HLA binding profiles for high-value targets. Here we present ESCAPE-seq (enhanced single-chain antigen presentation sequencing), a massively parallel platform for comprehensive screening of class I HLA–peptide combinations for antigen presentation via deep DNA sequencing. ESCAPE-seq demonstrates programmability, high throughput, sensitivity and nominated viral and cancer epitopes. We simultaneously assessed over 75,000 peptide–HLA combinations, revealing broadly presented epitopes from oncogenic driver mutations and fusions across diverse HLA-A, HLA-B and HLA-C alleles that cover 90% of the human population. We further identified epitopes that are differentially presented, comparing oncogenic hotspot mutations versus wild type. ESCAPE-seq enables one-shot population-wide antigen presentation discovery, offering insights into HLA specificity and immune recognition of genomic mutations.

DOI: 10.1038/s41588-025-02268-1

Source: https://www.nature.com/articles/s41588-025-02268-1