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Br J Cancer. 2018 Jan;118(1):62-71. doi: 10.1038/bjc.2017.389. Epub 2017 Nov 7.

Interferon regulatory factor 1 priming of tumour-derived exosomes enhances the antitumour immune response.

Author information

1
Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 15260, USA.
2
Department of General Surgery, Tenth People's Hospital affiliated to Tongji University, Shanghai 200072, China.
3
Department of Obstetrics, Gynecology, and Reproductive Sciences, Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA 15213, USA.
4
The Third Xiangya Hospital, Central South University, Changsha, Hunan 410000, China.
5
Center for Biologic Imaging, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.

Abstract

BACKGROUND:

Tumour-derived exosomes (TEXs) have a potential for application in cancer vaccines. Whether TEXs after induction by interferon regulatory factor 1 (IRF-1) are capable of enhancing the antitumour response remains to be determined.

METHODS:

Exosomes released by tumour cells infected with IRF-1-expressing adenovirus (IRF-1-Exo) or treated with interferon-γ (IFN-Exo) were isolated via ultracentrifugation. The IRF-1 target proteins IL-15Rα and MHC class I (MHC-I) were analysed by western blot. Exosomes along with CpG adjuvant were injected into tumour models to assess the antitumour effects. Tumours were harvested for immunofluorescence staining. Splenocytes from tumour-bearing mice were co-cultured with tumour cells. The IFNγ-positive and granzyme B-positive CD8α+ splenocyte cells were quantified by flow cytometry.

RESULTS:

The IRF-1-Exo or IFN-Exo displayed increased IL-15Rα and MHC-I expression. Injection of IRF-1-Exo or IFN-Exo combined with CpG had improved antitumour effects in mice. This effect may be a result of increased infiltration of tumours by CD4+ and CD8α+ T cells. Antibody-mediated depletion of CD4+ or CD8+ T cells abrogated the antitumour effects. Splenocytes isolated from CpG+IRF-1-Exo-injected Hepa 1-6 tumour mice had increased IFNγ-positive and granzyme B-positive CD8+ cells after co-culturing with Hepa 1-6 cells as compared with MC38 cells.

CONCLUSIONS:

The IRF-1 priming of TEXs enhances antitumour immune response.

PMID:
29112686
PMCID:
PMC5765230
DOI:
10.1038/bjc.2017.389
[Indexed for MEDLINE]
Free PMC Article

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