蛋白质基因组学分析揭示了RNA作为肿瘤不可知新抗原鉴定的来源。
Proteogenomic analysis reveals RNA as a source for tumor-agnostic neoantigen identification.
发表日期：2023 Aug 02
作者：
Celina Tretter, Niklas de Andrade Krätzig, Matteo Pecoraro, Sebastian Lange, Philipp Seifert, Clara von Frankenberg, Johannes Untch, Gabriela Zuleger, Mathias Wilhelm, Daniel P Zolg, Florian S Dreyer, Eva Bräunlein, Thomas Engleitner, Sebastian Uhrig, Melanie Boxberg, Katja Steiger, Julia Slotta-Huspenina, Sebastian Ochsenreither, Nikolas von Bubnoff, Sebastian Bauer, Melanie Boerries, Philipp J Jost, Kristina Schenck, Iska Dresing, Florian Bassermann, Helmut Friess, Daniel Reim, Konrad Grützmann, Katrin Pfütze, Barbara Klink, Evelin Schröck, Bernhard Haller, Bernhard Kuster, Matthias Mann, Wilko Weichert, Stefan Fröhling, Roland Rad, Michael Hiltensperger, Angela M Krackhardt
来源：
BIOMEDICINE & PHARMACOTHERAPY
摘要：
系统性的全肿瘤分析可能会揭示与癌症免疫原性和患者生存相关的常见特征的重要性。在这里，我们提供了一个包含32名患者、25种肿瘤类型的全面多组学数据集，用于基于蛋白质基因组学的新抗原的发现。通过使用优化的计算方法，我们发现了大量的肿瘤特异性和肿瘤相关抗原。为了在我们的队列中创建一个新抗原鉴定的流程，我们将DNA和RNA测序与肿瘤标本的基于质谱的免疫肽组学相结合，然后评估其免疫原性，并进行深入验证。我们在大部分患者中检测到广泛的非规范HLA结合肽，表明部分免疫原性。我们的验证过程允许选择32个潜在新抗原候选者。大多数新抗原候选者来自RNA数据集中鉴定的变异体，说明RNA作为一个尚未充分研究的癌症抗原来源的重要性。这项研究强调了以RNA为中心的变异体检测对于鉴定共享生物标志物和可能相关的新抗原候选者的重要性。© 2023. 作者。
Systemic pan-tumor analyses may reveal the significance of common features implicated in cancer immunogenicity and patient survival. Here, we provide a comprehensive multi-omics data set for 32 patients across 25 tumor types for proteogenomic-based discovery of neoantigens. By using an optimized computational approach, we discover a large number of tumor-specific and tumor-associated antigens. To create a pipeline for the identification of neoantigens in our cohort, we combine DNA and RNA sequencing with MS-based immunopeptidomics of tumor specimens, followed by the assessment of their immunogenicity and an in-depth validation process. We detect a broad variety of non-canonical HLA-binding peptides in the majority of patients demonstrating partially immunogenicity. Our validation process allows for the selection of 32 potential neoantigen candidates. The majority of neoantigen candidates originates from variants identified in the RNA data set, illustrating the relevance of RNA as a still understudied source of cancer antigens. This study underlines the importance of RNA-centered variant detection for the identification of shared biomarkers and potentially relevant neoantigen candidates.© 2023. The Author(s).