生物
人类白细胞抗原
PVT1型
CD8型
基因
免疫系统
癌症研究
基因组
癌症
核糖核酸
T细胞
抗原
长非编码RNA
肿瘤微环境
免疫疗法
计算生物学
病毒学
免疫学
遗传学
作者
Yasuhiro Kikuchi,Serina Tokita,Tomomi Hirama,Vitaly Kochin,Munehide Nakatsugawa,Tomoyo Shinkawa,Yoshihiko Hirohashi,Tomohide Tsukahara,Fumitake Hata,Ichiro Takemasa,Noriyuki Sato,Takayuki Kanaseki,Toshihiko Torigoe
出处
期刊:Cancer immunology research
[American Association for Cancer Research]
日期:2021-08-25
卷期号:9 (11): 1342-1353
被引量:10
标识
DOI:10.1158/2326-6066.cir-20-0964
摘要
Abstract CD8+ T cells recognize peptides displayed by HLA class I molecules on cell surfaces, monitoring pathologic conditions such as cancer. Advances in proteogenomic analysis of HLA ligandomes have demonstrated that cells present a subset of cryptic peptides derived from noncoding regions of the genome; however, the roles of cryptic HLA ligands in tumor immunity remain unknown. In the current study, we comprehensively and quantitatively investigated the HLA class I ligandome of a set of human colorectal cancer and matched normal tissues, showing that cryptic translation products accounted for approximately 5% of the HLA class I ligandome. We also found that a peptide encoded by the long noncoding RNA (lncRNA) PVT1 was predominantly enriched in multiple colorectal cancer tissues. The PVT1 gene is located downstream of the MYC gene in the genome and is aberrantly overexpressed across a variety of cancers, reflecting its oncogenic property. The PVT1 peptide was recognized by patient CD8+ tumor-infiltrating lymphocytes, as well as peripheral blood mononuclear cells, suggesting the presence of patient immune surveillance. Our findings show that peptides can be translated from lncRNAs and presented by HLA class I and that cancer patient T cells are capable of sensing aberrations in noncoding regions of the genome.
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