More efficient induction of antitumor T cell immunity by exosomes from CD40L gene-modified lung tumor cells

Abstract

The incidence of lung cancer increases annually. However, the effects of the present methods for the treatment of lung cancer are extremely poor. It has been reported that exosomes from heat‑stressed 3LL Lewis lung tumor cells effectively elicit systemic antitumor immunity. CD40 signaling is critical in the activation of dendritic cells(DCs), which are important in the induction of antitumor immunity. In the present study, exosomes from CD40 ligand gene‑modified 3LL tumor cells (CD40L‑EXO) were identified to be more immunogenic compared with control‑EXO and lac Z-EXO. CD40L‑EXO induced a more mature phenotype of the DCs and promoted them to secrete high levels of interleukin‑12. CD40L‑EXO‑treated DCs induced a greater proliferation of allogeneic Tcells in the mixed lymphocyte reaction. Moreover, CD40L‑EXO induced robust tumor antigen‑specific CD4+ Tcell proliferation exvivo. CD40L‑EXO were also extremely effective in the protective and therapeutic antitumor tests invivo. These results indicate that CD40L‑EXO may be used as an efficient vaccine for lung cancer immunotherapy.