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

Wang,Jiaoli; Wang,Limin; Lin,Zhendong; Tao,Lisha; Chen,Ming

doi:10.3892/mmr.2013.1759

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

Authors:
- Jiaoli Wang
- Limin Wang
- Zhendong Lin
- Lisha Tao
- Ming Chen
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Affiliations: Department of Respiratory Medicine, Hangzhou First People's Hospital, Hangzhou, Zhejiang 310006, P.R. China, Department of Orthopedics, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, P.R. China, Department of Gastroenterology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, P.R. China, Department of Otolaryngology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, P.R. China
Published online on: October 25, 2013 https://doi.org/10.3892/mmr.2013.1759
Pages: 125-131

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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 T cells in the mixed lymphocyte reaction. Moreover, CD40L‑EXO induced robust tumor antigen‑specific CD4+ T cell proliferation ex vivo. CD40L‑EXO were also extremely effective in the protective and therapeutic antitumor tests in vivo. These results indicate that CD40L‑EXO may be used as an efficient vaccine for lung cancer immunotherapy.

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