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未被注释的蛋白质扩大了癌症中MHC-I限制性的免疫肽组
2021-10-23 20:28

美国麻省理工学院Aviv Regev、哈佛大学Catherine J. Wu等研究人员合作发现,未被注释的蛋白质扩大了癌症中MHC-I限制性的免疫肽组。相关论文于2021年10月18日在线发表在《自然—生物技术》杂志上。

研究人员表明,通过对恶性和健康样本的核糖体分析检测到的新的或未被注释的开放阅读框(nuORF)肽可以展示在癌细胞的MHC-I上,作为癌症抗原的额外来源。研究人员构建了一个跨组织的高置信度nuORF数据库(nuORFdb),并使用它来检测MHC-I免疫肽组质谱分析中的3,555个翻译的nuORF,包括癌症样本nuORF的体细胞突变产生的肽,以及黑色素瘤、慢性淋巴细胞白血病和胶质母细胞瘤中翻译的肿瘤特定nuORF。nuORF是一个尚未开发的MHC-I呈递的肿瘤特异性肽库,具有作为免疫疗法靶点的潜力。

据了解,呈递在MHC-I上的并且能够激活免疫系统对抗癌细胞的肿瘤相关表位通常是由基因组中被注释的蛋白质编码区域确定的,但源于nuORF的肽是否能够促进抗肿瘤免疫反应仍不清楚。

附:英文原文

Title: Unannotated proteins expand the MHC-I-restricted immunopeptidome in cancer

Author: Ouspenskaia, Tamara, Law, Travis, Clauser, Karl R., Klaeger, Susan, Sarkizova, Siranush, Aguet, Franois, Li, Bo, Christian, Elena, Knisbacher, Binyamin A., Le, Phuong M., Hartigan, Christina R., Keshishian, Hasmik, Apffel, Annie, Oliveira, Giacomo, Zhang, Wandi, Chen, Sarah, Chow, Yuen Ting, Ji, Zhe, Jungreis, Irwin, Shukla, Sachet A., Justesen, Sune, Bachireddy, Pavan, Kellis, Manolis, Getz, Gad, Hacohen, Nir, Keskin, Derin B., Carr, Steven A., Wu, Catherine J., Regev, Aviv

Issue&Volume: 2021-10-18

Abstract: Tumor-associated epitopes presented on MHC-I that can activate the immune system against cancer cells are typically identified from annotated protein-coding regions of the genome, but whether peptides originating from novel or unannotated open reading frames (nuORFs) can contribute to antitumor immune responses remains unclear. Here we show that peptides originating from nuORFs detected by ribosome profiling of malignant and healthy samples can be displayed on MHC-I of cancer cells, acting as additional sources of cancer antigens. We constructed a high-confidence database of translated nuORFs across tissues (nuORFdb) and used it to detect 3,555 translated nuORFs from MHC-I immunopeptidome mass spectrometry analysis, including peptides that result from somatic mutations in nuORFs of cancer samples as well as tumor-specific nuORFs translated in melanoma, chronic lymphocytic leukemia and glioblastoma. NuORFs are an unexplored pool of MHC-I-presented, tumor-specific peptides with potential as immunotherapy targets. New tumor epitopes are discovered by ribosome profiling and immunopeptidome mass spectrometry.

DOI: 10.1038/s41587-021-01021-3

Source: https://www.nature.com/articles/s41587-021-01021-3

Nature Biotechnology:《自然—生物技术》,创刊于1996年。隶属于施普林格·自然出版集团,最新IF:68.164
官方网址:https://www.nature.com/nbt/
投稿链接:https://mts-nbt.nature.com/cgi-bin/main.plex


本期文章:《自然—生物技术》:Online/在线发表

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