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In Vivo Immunogenicity Screening of Tumor-Derived Extracellular Vesicles by Flow Cytometry of Splenic T Cells
Published on: September 23, 2021
Tumor Cell-associated Exosomes Robustly Elicit Anti-tumor Immune Responses through Modulating Dendritic Cell Vaccines
Ce Wang1,2, Xue Huang2, Yingjuan Wu2
1Department of anatomy, School of Medicine, Jinan University, Guangzhou 510632, China.
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.
Insights
Tumor-associated exosomes (TAEs) enhance dendritic cell (DC) vaccines, improving anti-tumor immunity in lung cancer. This novel approach boosts T cell responses and reduces regulatory T cells (Tregs), offering a promising cancer immunotherapy strategy.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- Dendritic cell (DC) vaccine immunotherapy shows promise for cancer treatment.
- Current DC vaccines using tumor cell lysates (TCLs) have limited antitumor effects due to poor immunogenicity.
- Tumor-associated exosomes (TAEs) are potential antigens for DC vaccines, but their role in lung cancer immunity is unclear.
Purpose of the Study:
- To investigate the efficacy of TAEs in enhancing DC vaccine immunogenicity and antitumor immunity in lung cancer.
- To compare the effects of TAEs versus TCLs on DC maturation and function.
- To evaluate the therapeutic potential of TAE-based DC vaccines (DCTAE) in vivo.
Main Methods:
- TAEs were extracted from tumor cell culture supernatant.
- TAEs and TCLs were used to stimulate DCs, and their effects on DC maturation and antigen presentation were assessed.
- Immunofluorescence, flow cytometry, and ELISA were used to evaluate tumor apoptosis, T cell responses (CD8+ T cells, Tregs), and cytokine levels (IL-12, IFN-γ, IL-10, TGF-β) in tumor-draining lymph nodes (TDLNs) and spleen.
- Tumor growth and survival rates were monitored in vivo.
Main Results:
- TAEs significantly promoted DC maturation and MHC cross-presentation compared to TCLs, leading to a stronger cytotoxic T lymphocyte (CTL) response.
- TAEs reduced PD-L1 expression on DCs, which in turn decreased regulatory T cell (Treg) populations in vitro.
- DCTAE administration suppressed tumor growth and improved survival rates in vivo, associated with increased CD8+ T cells and decreased Tregs.
Conclusions:
- TAEs are superior to TCLs for enhancing DC vaccine immunogenicity and eliciting robust antitumor immunity.
- TAE-based DC vaccines can modulate the tumor microenvironment by increasing anti-tumor T cell responses and reducing immunosuppressive Tregs.
- TAE-based DC vaccines represent a promising strategy for improving cancer immunotherapy outcomes.
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