Characterization and functional analysis of cancer-antigen specific tumour immune infiltrates from patients with head and neck squamous cell carcinoma

头颈鳞状细胞癌患者癌症抗原特异性肿瘤免疫浸润的特征和功能分析

• 批准号: 416718265
• 负责人: Privatdozent Dr. Adrian von Witzleben
• 金额: --
• 依托单位: Universitätsklinik für Hals-, Nasen- und Ohrenheilkunde
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/416718265?language=en
• 关键词: Characterization; functional; analysis; cancer; antigen

I) To characterize the phenotype and functional capability of CD8+ and CD4+ T-cells in different compartments of head and neck squamous cell carcinoma. To this end, immune cells from tissue samples of primary tumours, draining lymph nodes and the peripheral blood will be isolated. The primary focus will lie in the analysis of tissue resident memory cells, which are likely enriched for cancer antigen specificity. II) To understand the link between the T-cell recognition of mutated and shared target antigens, the density and composition of immune infiltrates and the presence of cancer-antigen specific immunity. The repertoire of potential target antigens in tumour biopsies will be characterized by whole tumour sequencing of exome DNA and total RNA. We will use bioinformatics pipelines established in Southampton to predict mutated neoantigens and to quantify the expression of shared cancer antigens (viral antigens, cancer-testis antigens). Tumour infiltrating immune cells from the respective patients will be expanded and tested for reactivity to selected target antigens. III) To determine the effect of neoadjuvant treatment with anti-PD-1 antibodies on tumour infiltrating immune cells. Experiments will be carried out in analogy to aim 2 in diagnostic pre-treatment biopsies and samples after neoadjuvant PD-1 antibody treatment from the time of surgical resection.

I）表征头颈部鳞状细胞癌的不同区室中的CD 8+和CD 4 + T细胞的表型和功能能力。为此，将从原发性肿瘤、引流淋巴结和外周血的组织样品中分离免疫细胞。主要焦点将在于组织驻留记忆细胞的分析，这些细胞可能富含癌症抗原特异性。II）了解T细胞识别突变和共享靶抗原、免疫浸润的密度和组成以及癌症抗原特异性免疫的存在之间的联系。肿瘤活检中潜在靶抗原的库将通过外显子组DNA和总RNA的全肿瘤测序来表征。我们将使用在南安普顿建立的生物信息学管道来预测突变的新抗原，并量化共享的癌症抗原（病毒抗原，癌症睾丸抗原）的表达。将扩增来自相应患者的肿瘤浸润免疫细胞，并测试其对选定靶抗原的反应性。III）确定用抗PD-1抗体进行新辅助治疗对肿瘤浸润免疫细胞的影响。将在诊断性治疗前活组织检查和新辅助PD-1抗体治疗后的样品中从手术切除时起类似于目的2进行实验。

项目成果

Prospective longitudinal study of immune checkpoint molecule (ICM) expression in immune cell subsets during curative conventional therapy of head and neck squamous cell carcinoma (HNSCC)

• DOI: 10.1002/ijc.33446
• 发表时间: 2020-12
• 期刊: International Journal of Cancer
• 影响因子: 6.4
• 作者: A. von Witzleben;A. Fehn;A. Grages;J. Ezić;S. Jeske;L. Puntigam;C. Brunner;J. Kraus;H. Kestler;J. Doescher;M. Brand;M. Theodoraki;C. Ottensmeier;T. Hoffmann;P. Schuler;S. Laban

Immune checkpoint expression in HNSCC patients before and after definitive chemoradiotherapy

• DOI: 10.1002/hed.26534
• 发表时间: 2020-11-06
• 期刊: HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK
• 影响因子: 2.9
• 作者: Doescher, Johannes;Minkenberg, Peter;Weissinger, Stephanie Ellen
• 通讯作者: Weissinger, Stephanie Ellen