Modeling NK-cell lymphoma in mice

An important limitation of the field is the lack of a genetically engineered mouse model (GEMM) recapitulating genetic events in human extranodal NK/T-cell lymphoma (ENKTCL). Although cell lines and xenografts have been developed in ENKTCL, these models are heterogenous and unable to reproduce the tumor immune microenvironment. To model ENKTCL in mice, here we have generated GEMM harboring NK-cell-specific Trp53 deletion. This model develops NK-cell lymphomas preferentially involving the salivary glands, which is accelerated by LMP1 expression. These models enable us to explore the cell-of-origin, microenvironmental changes, and therapeutic targets of ENKTCL.