Differential immunopeptidome analysis revealed cancer specific amino acid usage of HLA class-I antigens and novel neoantigens of colorectal cancer
Differential immunopeptidome analysis revealed cancer specific amino acid usage of HLA class-I antigens and novel neoantigens of colorectal cancer
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差异免疫肽组分析揭示了 HLA I 类抗原和结直肠癌新抗原的癌症特异性氨基酸使用
DOI：
10.1101/2021.04.09.439118
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Koji Ueda
中科院分区：
文献类型：
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作者：
Yuriko Minegishi;Kazuma Kiyotani;Kensaku Nemoto;Yoshikage Inoue;Yoshimi Haga;Risa Fujii;Naomi Saichi;Satoshi Nagayama;Koji Ueda
了解人类白细胞抗原（HLA）肽（也称为免疫肽）的性质对于实现癌症精准医疗（例如癌症疫苗接种）和更好地预测免疫检查点抑制剂（ICI）治疗的疗效至关重要。通过质谱 (MS) 直接检测免疫肽对于此目的非常有用，但在分析稀缺组织样本时仍然面临技术挑战。为了阐明结直肠癌（CRC）特异性呈现的HLA I类免疫肽的特征，建立了优化的免疫肽分离方法和基于全外显子组测序（WES）的差分离子淌度质谱（DIM-MS）个性化数据库，并对CRC患者的肿瘤或正常组织进行差异分析。通过使用 108 个结肠癌细胞系 HCT116 细胞的初步实验，鉴定出总共 9,249 种独特的免疫肽，其中包括总共 11 种新抗原。接下来，从 17 名患者身上收集了大约 40 毫克肿瘤或正常区域的 CRC 组织，并通过我们的个性化免疫肽组学技术进行分析。结果，对 44,785 个独特的免疫肽进行了分析，其中鉴定出 2 个携带 KRAS-G12V 或 CPPED1-R228Q 突变的新抗原。有趣的是，在肿瘤特异性免疫肽中发现了免疫肽 C 端修剪的特定氨基酸使用。因此，我们的个性化免疫肽组分析显着扩展了抗原知识库，并允许从稀有组织标本中直接测定新抗原。这种先进的免疫肽组学为免疫肽的基础和临床研究带来了新的前景。
Knowing the nature of human leukocyte antigen (HLA) peptides, also called as immunopeptides, is indispensable to realize the cancer precision medicine such as cancer vaccination and the better prediction of efficacy for immunocheckpoint inhibitor (ICI) treatment. Direct interrogation of immunopeptides by mass spectrometry (MS) is of great use for that purpose but the reality in analyses of scarce tissue samples still confronts technical challenges. To elucidate characteristics of HLA class-I immunopeptides specifically presented on colorectal cancer (CRC), the optimized immunopeptide isolation method and differential ion mobility mass spectrometry (DIM-MS) with whole exome sequencing (WES)-based personalized database were established and subjected to differential analysis of tumor or normal tissues of CRC patients. From pilot experiments using 108cells of colon cancer cell line HCT116, total 9,249 unique immunopeptides, including total 11 neoantigens, were identified. Next, approximately 40 mg of tumor or normal regions of CRC tissues were collected from 17 patients and analyzed by our personalized immunopeptidomic technology. As the result, 44,785 unique immunopeptides were profiled, in which 2 neoantigens carrying the mutation KRAS-G12V or CPPED1-R228Q were identified. Interestingly, specific amino acid usage of C-terminus trimming of immunopeptides was found in tumor-exclusive immunopeptides. Thus, our personalized immunopeptidome analysis significantly expands presented antigen knowledgebase and allows direct determination of neoantigens from scarce tissue specimens. This advanced immunopeptidomics holds promise to new outlook of research in immunopeptides both from basic and clinical aspects.