研究动态
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口咽鳞状细胞癌的HLA配基体组成分析揭示了共享的仅肿瘤特异性肽段,为半个性化疫苗的接种提供了基础。

The HLA ligandome of oropharyngeal squamous cell carcinomas reveals shared tumour-exclusive peptides for semi-personalised vaccination.

发表日期:2023 Feb 23
作者: Lena Mühlenbruch, Tsima Abou-Kors, Marissa L Dubbelaar, Leon Bichmann, Oliver Kohlbacher, Martin Bens, Jaya Thomas, Jasmin Ezić, Johann M Kraus, Hans A Kestler, Adrian von Witzleben, Joannis Mytilineos, Daniel Fürst, Daphne Engelhardt, Johannes Doescher, Jens Greve, Patrick J Schuler, Marie-Nicole Theodoraki, Cornelia Brunner, Thomas K Hoffmann, Hans-Georg Rammensee, Juliane S Walz, Simon Laban
来源: BRITISH JOURNAL OF CANCER

摘要:

OPSCC的免疫肽组在先前并未进行研究。癌抗原特异性疫苗可能会改善临床结果和PD1/PD-L1抗体等免疫检查点抑制剂的疗效。通过质谱(MS)分析自然表达的HLA配体从OPSCC肿瘤组织样本(n = 40)中获得映射OPSCC HLA配体组。该队伍包括22个HPV阳性(主要是HPV-16)和18个HPV阴性样本。使用HLA配体组的良性参考数据集识别肿瘤相关抗原。MS分析导致在OPSCC肿瘤组织中鉴定了天然HLA呈现的肽。总共在HLA-I类中检测到来自9485个源蛋白的22,769个肽,对于HLA-II类来说,则发现了来自4634个源蛋白的15,203个肽。通过与良性HLA配体组数据集进行比较分析,选择了覆盖11种不同HLA所有型的29个OPSCC相关HLA-I类配体和9个HLA-II类配体,以创建肽库。肿瘤相关肽在OPSCC的细胞表面上HLA呈现。建立的OPSCC相关肽库可用于下游免疫原性测试和基于肽的(半)个性化策略中的免疫治疗。©2023年。作者。
The immune peptidome of OPSCC has not previously been studied. Cancer-antigen specific vaccination may improve clinical outcome and efficacy of immune checkpoint inhibitors such as PD1/PD-L1 antibodies.Mapping of the OPSCC HLA ligandome was performed by mass spectrometry (MS) based analysis of naturally presented HLA ligands isolated from tumour tissue samples (n = 40) using immunoaffinity purification. The cohort included 22 HPV-positive (primarily HPV-16) and 18 HPV-negative samples. A benign reference dataset comprised of the HLA ligandomes of benign haematological and tissue datasets was used to identify tumour-associated antigens.MS analysis led to the identification of naturally HLA-presented peptides in OPSCC tumour tissue. In total, 22,769 peptides from 9485 source proteins were detected on HLA class I. For HLA class II, 15,203 peptides from 4634 source proteins were discovered. By comparative profiling against the benign HLA ligandomic datasets, 29 OPSCC-associated HLA class I ligands covering 11 different HLA allotypes and nine HLA class II ligands were selected to create a peptide warehouse.Tumour-associated peptides are HLA-presented on the cell surfaces of OPSCCs. The established warehouse of OPSCC-associated peptides can be used for downstream immunogenicity testing and peptide-based immunotherapy in (semi)personalised strategies.© 2023. The Author(s).