The Role of LLT1 (CLEC2D, OCIL) in Ewing Sarcoma

Ewing Sarcoma (EWS) is a pediatric bone cancer that is characterized by a chromosomal translocation giving rise to a neomorphic gene fusion. Although treatment of EWS has a 5-year incident free survival rate of 66%, treatment has plateaued since the 1980's. Natural killer (NK) cells are an important innate immune cell due to their ability to recognize and lyse virally infected and cancerous cells. Unfortunately, cancerous cells often employ strategies such as the downregulation of major histocompatibility complex (MHC) I, or upregulation of inhibitory ligands enabling the escape of T-cells and NK cell mediated killing. LLT1 is an inhibitory ligand our lab had previously shown that it is expressed on TNBC and prostate cancer cell lines. The expression of LLT1 and its function in Ewing Sarcoma (EWS) cell lines has yet to be performed. Our hypothesis is that LLT1 is increased in EWS cell lines TC-32 and CHLA-258 when treated with chemotherapeutic drugs vincristine and etoposide. Our results show that LLT1 is expressed on EWS cell lines and inhibition of LLT1 increases NK cell cytotoxicity. These results indicate that LLT1 is a potential immunotherapy target that needs to be further evaluated in an in vivo model.