Modulation of immune checkpoint molecule expression in mantle cell lymphoma

AbstractMantle cell lymphoma (MCL) is an aggressive B-cell malignancy for which novel therapeutics with improved efficacy are greatly needed. To provide support for clinical immune checkpointblockade, we comprehensively evaluated the expression of therapeutically targetable immune checkpointmolecules on primary MCL cells. MCL cells showed constitutive expression of Programmed Death 1 (PD-1) and Programmed Death Ligand 1 ( PD-L1), variable CD200, absent PD-L2, Lymphocyte Activation Gene 3 (LAG-3), and Cytotoxic T-cellAssociated Protein 4 ( CTLA-4). Effector cellsfrom MCL patients expressed PD-1. Co-culture of MCL cells with T-cells induced PD-L1surface expression, a phenomenon regulated by IFNγ and CD40:CD40L interaction. Induction of PD-L1was attenuated by concurrent treatment with ibrutinibor duvelisib, suggesting BTK and PI3K are important mediators of PD-L1expression. Overall, our data provide further insight into the expression of checkpoint molecules in MCL and support the use of PD-L1blocking...