The Role of Hvem and its Interaction with Btla and Cd160 in b-Cell Lymphoma Progression

Abstract

SUMMARYDespite the fact that the cell surface receptor HVEM (TNFRSF14) appears to be implicated in the development and progression of B-cell lymphomas, its specific role in these tumours is still unclear. On the one hand, HVEM over-expression is related to worse prognosis in some types of B-cell lymphoma and other solid tumours. On the other hand, most mutations of HVEM in B-cell lymphomas are thought to promote tumour growth through the loss of function. Here, we used a CRISPR-Cas9 system to study the effect of HVEM loss on gene expression in a murine model of A20 B-cell lymphoma (belonging to the diffuse large B-cell lymphoma group). We show that loss of HVEM does not affect the doubling rate of A20 tumour cells in culture, but leads to a decrease in BTLA expression. HVEM-deficient A20 cells do not present a different pattern of metastatic dissemination to lymphoid organs compared with unmodified A20 cells. However, we observed a significant expansion of endogenous B-cells as a result of A20 tumour implantation in the thymus. Although we found no differences in the dissemination or progression of HVEM-deficient A20 cells, our results reveal that loss of HVEM alters the leukocyte recruitment capacity of A20 cells in hepatic tumour nodules at the intermediate stage of tumour development, which may be of relevance as a mechanism of immune evasion.