Aberrant Cathepsin S (CTSS) Activity in Follicular Lymphoma (P04)

滤泡性淋巴瘤中组织蛋白酶 S (CTSS) 活性异常 (P04)

• 批准号: 405441245
• 金额: --
• 依托单位: Medizinische Klinik und Poliklinik III - Großhadern
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/405441245?language=en
• 关键词: Aberrant; Cathepsin; CTSS; Activity; Follicular

We discovered a clinically relevant mechanism of tumour and immune cell interaction in follicular lymphoma, a prototypical type of blood cancer. Cathepsin S (CTSS) alterations result in aberrant hyperactivity of this lysosomal cysteine protease and induce a tumour-promoting CD4 T cell enriched immune microenvironment. We use innovative ex vivo and in vivo models to functionally define and therapeutically target these tumour-promoting interactions. Furthermore, we identified intriguing roles of CTSS in NF-κB and TLR signalling, and -unexpectedly- in the nucleus. Defining and targeting the unique pathobiology of CTSS hyperactive tumours is expected to provide a strong rationale for its translation into the clinic.

我们在滤泡性淋巴瘤（一种典型的血癌）中发现了肿瘤和免疫细胞相互作用的临床相关机制。组织蛋白酶S （CTSS）的改变导致这种溶酶体半胱氨酸蛋白酶异常亢进，并诱导促进肿瘤的CD4 T细胞富集免疫微环境。我们使用创新的离体和体内模型来功能定义和治疗这些促进肿瘤的相互作用。此外，我们确定了CTSS在NF-κ b和TLR信号传导中的有趣作用，以及-出乎意料的-在细胞核中的作用。定义和靶向CTSS过度活跃肿瘤的独特病理生物学有望为其转化为临床提供强有力的理论依据。