German Cancer Consortium (DKTK), partner site Munich and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Technical University of Munich, TUM School of Medicine, Klinikum rechts der Isar, IIIrd Medical Department, Munich, Germany.
Nat Commun. 2023 Aug 2;14(1):4632. doi: 10.1038/s41467-023-39570-7.
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.
系统的泛肿瘤分析可能揭示癌症免疫原性和患者生存中常见特征的意义。在这里，我们提供了一个包含 32 名患者 25 种肿瘤类型的综合多组学数据集，用于基于蛋白质基因组学的新抗原发现。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识别新抗原的管道，我们将 DNA 和 RNA 测序与肿瘤标本的基于 MS 的免疫肽组学相结合，然后评估它们的免疫原性和进行深入的验证过程。我们在大多数表现出部分免疫原性的患者中检测到大量非典型 HLA 结合肽。我们的验证过程允许选择 32 个潜在的新抗原候选物。大多数新抗原候选物来源于 RNA 数据集识别的变体，这表明 RNA 作为一个研究较少的癌症抗原来源的重要性。这项研究强调了基于 RNA 的变异检测对于识别共享生物标志物和潜在相关新抗原候选物的重要性。
