Hdac6 Inhibition Increases Translation Of Cd20 Mrna And Potentiates The Efficacy Of Anti-Cd20 Immunotherapy

Down-regulation of CD20, a molecular target for monoclonal antibodies, is a clinical problem leading to decreased efficacy of anti-CD20-based regimens. Moreover, a substantial number of patients do not fully benefit from anti-CD20 immunotherapy due to the low CD20 expression. It has been shown that histone deacetylase inhibitors (HDACi), in a transcription-dependent mechanism, regulate CD20 surface level. However, non-specific HDAC pan-inhibitors have considerable number of side effects, therefore a new isoform-specific inhibitors are being developed. Recently, HDAC6-selective inhibitors have emerged in non-Hodgkin lymphoma and chronic lymphocytic leukemia (CLL) potential therapies. Preclinical data show therapeutic potential of HDAC6 inhibitors in combination approach. However, their effect on the efficacy of anti-CD20 immunotherapy has not been studied so far. Therefore, this study aimed to investigate the influence of HDAC6 inhibition on the regulation of CD20 expression.