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

我们发现了滤泡性淋巴瘤与免疫细胞相互作用的临床相关机制，滤泡性淋巴瘤是一种典型的血癌类型。组织蛋白酶S(CTs)的改变导致这种溶酶体半胱氨酸蛋白酶的异常高活性，并诱导了促进肿瘤的CD4T细胞丰富的免疫微环境。我们使用创新的体外和体内模型来从功能上定义和治疗这些促进肿瘤的相互作用。此外，我们还发现了CTSS在核转录因子-κB和TLR信号通路中的有趣作用，以及--出乎意料的--在细胞核中。定义和定位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基础。

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.