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Tumor Cell-associated Exosomes Robustly Elicit Anti-tumor Immune Responses through Modulating Dendritic Cell Vaccines in Lung Tumor
- Source :
- International Journal of Biological Sciences
- Publication Year :
- 2019
-
Abstract
- DC vaccine-based immunotherapy is emerging as a novel therapeutic strategy for cancer treatment, however, antitumor effect of DC vaccines based on tumor cell lysates (TCLs) remains unsatisfactory due to poor immunogenicity of tumor antigens. Although tumor-associated exosomes (TAEs) have been reported as a promising antigen for DC vaccines, it remains unclear how TAE-based DC vaccine induced antitumor immunity in lung cancer. Methods: In the present study, we extracted TAEs from the supernatant of tumor cell culture medium, and compared the effect of TAEs with TCLs on DCs. To further evaluate the therapeutic effect of DCTAE, we used immunofluorescence and flow cytometry to evaluate the apoptosis of tumor tissue, tumor-infiltrating CD8+ T cells and Tregs in TDLNs and spleen. Then the levels of cytokines of IL-12, IFN-γ, L-10 and TGF-β were quantified by ELISA assays. Results: Our data showed that TAEs were more potent than TCLs to promote DC maturation and enhance MHC cross presentation, which directly contributed to more robust tumor-specific cytotoxic T lymphocyte (CTL) response. More importantly, TAEs reduced the expression of PD-L1 of DCs, thereby led to down-regulated population of Tregs in vitro. Moreover, DCTAE remarkably suppressed the tumor growth and prolonged survival rate in vivo, due to participance of CD8+ T cells and decreased Tregs in TDLNs and spleen. Conclusion: TAEs could serve to improve vaccine-elicited immunotherapy by triggering stronger DC-mediated immune responses and decreasing Tregs in the tumor microenvironment.
- Subjects :
- Lung Neoplasms
medicine.medical_treatment
Blotting, Western
CD8-Positive T-Lymphocytes
Exosomes
Applied Microbiology and Biotechnology
Cancer Vaccines
T-Lymphocytes, Regulatory
immune response
DC vaccine
lung tumor
03 medical and health sciences
Mice
Immune system
Antigen
In Situ Nick-End Labeling
Medicine
Cytotoxic T cell
Animals
Humans
tumor cell-associated exosome
Molecular Biology
Ecology, Evolution, Behavior and Systematics
030304 developmental biology
0303 health sciences
Tumor microenvironment
immunosuppression
business.industry
Cross-presentation
Cell Biology
Dendritic cell
Immunotherapy
Dendritic Cells
Mice, Inbred C57BL
A549 Cells
Cancer research
Female
business
CD8
Developmental Biology
Research Paper
Subjects
Details
- ISSN :
- 14492288
- Volume :
- 16
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- International journal of biological sciences
- Accession number :
- edsair.doi.dedup.....eebc22a15a239058f82a801993dfaf9b