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

我们发现了滤泡性淋巴瘤（一种典型的血癌）中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）改变导致该溶酶体半胱氨酸蛋白酶的异常高活性，并诱导肿瘤促进性CD 4 T细胞富集的免疫微环境。我们使用创新的离体和体内模型来功能性地定义和治疗靶向这些肿瘤促进相互作用。此外，我们确定了CTSS在NF-κB和TLR信号传导中的有趣作用，并且-出乎意料地-在细胞核中。定义和靶向CTSS过度活跃肿瘤的独特病理生物学，预计将为其转化为临床提供强有力的理由。

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.