Combination lenalidomide-rituximab immunotherapy activates anti-tumour immunity and induces tumour cell death by complementary mechanisms of action in follicular lymphoma.

ABSTRACT: Chemotherapy plus rituximab has been the mainstay of treatment for follicular lymphoma (FL) for two decades but is associated with immunosuppression and relapse. In phase 2 studies, lenalidomide combined with rituximab (R² ) has shown clinical synergy in front-line and relapsed/refractory FL. Here, we show that lenalidomide reactivated dysfunctional T and Natural Killer (NK) cells ex vivo from FL patients by enhancing proliferative capacity and T-helper cell type 1 (Th1) cytokine release. In combination with rituximab, lenalidomide improved antibody-dependent cellular cytotoxicity in sensitive and chemo-resistant FL cells, via a cereblon-dependent mechanism. While single-agent lenalidomide and rituximab increased formation of lytic NK cell immunological synapses with primary FL

SUBMITTER: Chiu H 

PROVIDER: S-EPMC6594227 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature