HBx induces chemoresistance in diffuse large B cell lymphoma by inhibiting intrinsic apoptosis via the NF-κB/XIAP pathway.

Diffuse large B cell lymphoma (DLBCL) is the predominant subtype of malignant lymphoma in adults with high heterogeneity. Hepatitis B virus (HBV) has been shown to infect B lymphocytes and has been associated with a higher risk of developing DLBCL, most clearly in countries where HBV is endemic. Accumulating evidence suggests that the standard chemotherapy regimens for DLBCL patients with HBV infection exhibit limited efficacy and unfavorable outcomes. The HBx antigen, encoded by the X gene in the four open reading frames of HBV, may be a key molecule promoting the heightened malignant biological characteristics of DLBCL, but whether it affects the chemotherapy response and the mechanism in DLBCL remains unclear. Through the implementation of in vitro and in vivo experiments, our study demonstrates that the HBx antigen triggers excessive activation of the NF-κB pathway, resulting in increased expression of the X-linked inhibitor of apoptosis protein (XIAP). This upregulation inhibits caspase-3-mediated intrinsic apoptosis and enhances resistance to first-line chemotherapeutic agents like epirubicin and vincristine in DLBCL. These findings offer insights into the development of innovative combination therapies for DLBCL patients with HBV infection.