Aberrant Cathepsin S activity in follicular lymphoma

  

Project Summary


We identified novel and recurrent hotspot mutations in Cathepsin S (CTSS) as a previously unrecognized link between aberrant intracellular immune signaling and the immune microenvironment in follicular lymphoma (FL). CTSS is a cysteine protease that is highly expressed in immune cells and plays critical roles in antigen presentation and Toll-like receptor (TLR) signaling. Our previous data show that these mutations are gain-of-function and activate tumor-promoting pathways, including deregulation of TLR and MHC-II signaling. Our project will utilize in vitro and in vivo models to define the underlying molecular mechanisms, as well as the functional and clinical implications of aberrant CTSS activity in FL.