Identification of tumor and stroma antigens for the treatment of HNSCC

鉴定用于治疗 HNSCC 的肿瘤和基质抗原

• 批准号: 240733925
• 负责人: Professor Dr. Philipp Beckhove
• 金额: --
• 依托单位: Neurochirurgische Klinik
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2016-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/240733925?language=en
• 关键词: Identification; tumor; stroma; antigens; treatment

Head and neck squamous cell carcinoma is a frequent cancer and associated with poor prognosis. Therefore, new therapeutic strategies are urgently required for this tumor entity. Cancer immunotherapy has recently emerged as a promising treatment modality in a number of cancers and may also improve clinical outcome in HNSCC patients. In other cancer types spontaneous tumor-specific T cell responses are correlated with increased T cell infiltration in tumors, improved prognosis and response to treatment and may thus represent a promising resource for cancer immunotherapy. For HNSCC we found that spontaneous tumor specific T cell responses as well as T cell infiltration are also associated with an improved prognosis. However, in order to clinically exploit the endogeneous repertoire of tumor reactive T cells for diagnosis and treatment, determination of the target antigens of such responses is mandatory. We have recently developed a novel technology that for the first time allows an unbiased and comprehensive identification of T cell target antigens in tumor tissues, which is not restricted to tumor cell-associated antigens but can also be used to identify tumor stroma-associated antigens. Within this project we will determine major target antigens of spontaneous T cell responses in the tumor tissue of HNSCC patients and assess in particular the role of tumor-associated fibroblasts as targets of protective T cell immunity since they are not subjected to immune editing, are homogeneously expressed throughout on the whole tumor tissue and since the tumor stroma is indispensable for tumor maintenance and progression. By T cell receptor (TCR) sequencing we will determine whether T cells specific for selected tumor cell- and fibroblast-associated antigens accumulate within the tumor tissue. We will characterize expression of selected major T cell target antigens in a larger cohort of HNSCC tumors and finally assess their prognostic relevance for overall survival. On this basis, we will select a panel of HNSCC-associated antigens with potential relevance for T cell based cancer immunotherapy.

头颈部鳞状细胞癌是一种常见的癌症，预后较差。因此，迫切需要新的治疗策略来治疗这种肿瘤。癌症免疫治疗最近已经成为一种很有前途的治疗方法，可用于多种癌症，也可改善HNSCC患者的临床预后。在其他类型的癌症中，自发的肿瘤特异性T细胞反应与肿瘤中T细胞浸润的增加、预后的改善和治疗反应有关，因此可能是癌症免疫治疗的一个有前途的来源。对于HNSCC，我们发现自发的肿瘤特异性T细胞反应和T细胞浸润也与改善预后有关。然而，为了在临床上开发内源性肿瘤反应性T细胞用于诊断和治疗，确定这种反应的靶抗原是强制性的。我们最近开发了一种新的技术，首次实现了对肿瘤组织中T细胞靶抗原的无偏见和全面的鉴定，这不仅限于肿瘤细胞相关抗原，而且还可以用于鉴定肿瘤间质相关抗原。在这个项目中，我们将确定HNSCC患者肿瘤组织中自发T细胞反应的主要靶抗原，并特别评估肿瘤相关成纤维细胞作为保护性T细胞免疫靶标的作用，因为它们不受免疫编辑，在整个肿瘤组织中均匀表达，而且肿瘤间质对于肿瘤的维持和发展是不可或缺的。通过T细胞受体(TCR)测序，我们将确定针对选定的肿瘤细胞和成纤维细胞相关抗原的T细胞是否在肿瘤组织中积聚。我们将研究选定的主要T细胞靶抗原在较大的HNSCC肿瘤队列中的表达特征，并最终评估它们与总生存率的预后相关性。在此基础上，我们将选择一组可能与T细胞为基础的癌症免疫治疗相关的HNSCC相关抗原。