| Description |
Tumor-derived exosomes (TEXs) enriched in immune suppressive molecules predominantly drive T cell dysfunction and impair anti-tumor immunity. Meanwhile, chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising treatment for refractory and relapsed hematological malignancies including lymphoma. Therefore, whether lymphoma TEXs have the impact upon the function of CAR T cell remains to be elucidated. In this study, we demonstrated that lymphoma-derived TEX induces the activation of CAR T cells, which is dependent on exosomal CD19 molecule stimulation. CD19 CAR T cells short term primed with Raji-TEXs are therapeutically superior to unprimed CAR T cells in a mice model of Raij Rab27a-/- cells. However, lymphoma TEX may subsequently induces CAR T cell apoptosis and impair tumor cytotoxicity of CAR T cells with upregulated expression of inhibitory receptors PD-1, TIM3, and LAG3 under longer exposure. More importantly, ScRNA-seq revealed that CAR T cells typically showed more differentiated phenotypes and conversiong of Treg phenotype. |
