Epstein-Barr virus (EBV) is a ubiquitous oncogenic virus that is associated with 
B cell lymphomas, including Burkitt lymphoma and Hodgkin lymphoma. Previous 
studies have shown that the phosphatidylinositol 3-kinase (PI3K)/Akt pathway is 
activated in EBV-associated lymphomas and can be a novel therapeutic target. An 
oral dual inhibitor of PI3Kγ and PI3Kδ, duvelisib, is in clinical trials for the 
treatment of lymphoid malignancies. In this study, we evaluated how duvelisib 
affects the activity of the PI3K/Akt signaling pathway and if it has antitumor 
effects in EBV-associated lymphoma cell lines. We found that the PI3K/Akt 
signaling pathway was activated in most of the B and T cell lymphoma cell lines 
tested. Additionally, duvelisib treatment inhibited cellular growth in the 
tested cell lines. Overall, B cell lines were more susceptible to duvelisib than 
T and NK cell lines in vitro regardless of EBV infection. However, the 
additional influence of duvelisib on the tumor microenvironment was not 
assessed. Duvelisib treatment induced both apoptosis and cell cycle arrest in 
EBV-positive and -negative B cell lines, but not in T cell lines. Furthermore, 
duvelisib treatment reduced the expression of EBV lytic genes (BZLF1 and 
gp350/220) in EBV-positive B cell lines, suggesting that duvelisib suppresses 
the lytic cycle of EBV induced by B cell receptor signaling. However, duvelisib 
did not induce a remarkable change in the expression of EBV latent genes. These 
results may indicate that there is therapeutic potential for duvelisib 
administration in the treatment of EBV-associated B cell lymphomas and other B 
cell malignancies.