Comparison of Exosomes Derived from Non- and Gamma-Irradiated Melanoma Cancer Cells as a Potential Antigenic and Immunogenic Source for Dendritic Cell-Based Immunotherapeutic Vaccine
Cancer cells can secrete exosomes under various stressful conditions, whose functions are involved in the delivery of various biologically active materials into host cells and/or modulation of host immune responses. Therefore, an improved understanding of the immunological interventions that stress-...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-11-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/8/4/699 |
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| author | Woo Sik Kim DaeSeong Choi Ji Min Park Ha-Yeon Song Ho Seong Seo Dong-Eun Lee Eui-Baek Byun |
| author_facet | Woo Sik Kim DaeSeong Choi Ji Min Park Ha-Yeon Song Ho Seong Seo Dong-Eun Lee Eui-Baek Byun |
| author_sort | Woo Sik Kim |
| collection | DOAJ |
| description | Cancer cells can secrete exosomes under various stressful conditions, whose functions are involved in the delivery of various biologically active materials into host cells and/or modulation of host immune responses. Therefore, an improved understanding of the immunological interventions that stress-induced tumor exosomes have may provide novel therapeutic approaches and more effective vaccine designs. Here, we confirmed the phenotypical and functional alterations of dendritic cells (DCs), which act as a bridge between the innate and adaptive arms of immunity, following non-irradiated (N-exo) and gamma-irradiated melanoma cancer cell-derived exosome (G-exo) stimulation, and evaluated the N-exo- and G-exo-stimulated DCs as therapeutic cancer vaccine candidates. We demonstrated that G-exo-stimulated DCs result in DC maturation by the upregulation of surface molecule expression, pro-inflammatory cytokine release, and antigen-presenting ability, and the downregulation of endocytic capacity. In addition, these cells promoted T cell proliferation and the generation of T helper type 1 (Th1) and interferon (IFN)-γ-producing CD8<sup>+</sup> T cells. However, N-exo-stimulated DCs induced semi-mature phenotypes and functions, eventually inhibiting T cell proliferation, decreasing IFN-γ, and increasing IL-10-producing CD4<sup>+</sup> T cells. In addition, although N-exo and G-exo stimulations showed similar levels of antigen-specific IFN-γ production, which served as tumor antigen sources in melanoma-specific T cells, G-exo-stimulated DC vaccination conferred a stronger tumor growth inhibition than N-exo-stimulated DC vaccination; further, this was accompanied by a high frequency of tumor-specific, multifunctional effector T cells. These results suggest that gamma irradiation could provide important clues for designing and developing effective exosome vaccines that can induce strong immunogenicity, especially tumor-specific multifunctional T cell responses. |
| first_indexed | 2024-03-10T14:43:25Z |
| format | Article |
| id | doaj.art-ead3731662574ab6b9008a5ae7c17a8a |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-10T14:43:25Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-ead3731662574ab6b9008a5ae7c17a8a2023-11-20T21:36:54ZengMDPI AGVaccines2076-393X2020-11-018469910.3390/vaccines8040699Comparison of Exosomes Derived from Non- and Gamma-Irradiated Melanoma Cancer Cells as a Potential Antigenic and Immunogenic Source for Dendritic Cell-Based Immunotherapeutic VaccineWoo Sik Kim0DaeSeong Choi1Ji Min Park2Ha-Yeon Song3Ho Seong Seo4Dong-Eun Lee5Eui-Baek Byun6Research Division for Radiation Science, Korea Atomic Energy Research Institute, Jeongeup 56212, KoreaResearch Division for Radiation Science, Korea Atomic Energy Research Institute, Jeongeup 56212, KoreaGeneral Toxicology Research Center, Korea Institute of Toxicology, Jeongup 56212, KoreaResearch Division for Radiation Science, Korea Atomic Energy Research Institute, Jeongeup 56212, KoreaResearch Division for Radiation Science, Korea Atomic Energy Research Institute, Jeongeup 56212, KoreaResearch Division for Radiation Science, Korea Atomic Energy Research Institute, Jeongeup 56212, KoreaResearch Division for Radiation Science, Korea Atomic Energy Research Institute, Jeongeup 56212, KoreaCancer cells can secrete exosomes under various stressful conditions, whose functions are involved in the delivery of various biologically active materials into host cells and/or modulation of host immune responses. Therefore, an improved understanding of the immunological interventions that stress-induced tumor exosomes have may provide novel therapeutic approaches and more effective vaccine designs. Here, we confirmed the phenotypical and functional alterations of dendritic cells (DCs), which act as a bridge between the innate and adaptive arms of immunity, following non-irradiated (N-exo) and gamma-irradiated melanoma cancer cell-derived exosome (G-exo) stimulation, and evaluated the N-exo- and G-exo-stimulated DCs as therapeutic cancer vaccine candidates. We demonstrated that G-exo-stimulated DCs result in DC maturation by the upregulation of surface molecule expression, pro-inflammatory cytokine release, and antigen-presenting ability, and the downregulation of endocytic capacity. In addition, these cells promoted T cell proliferation and the generation of T helper type 1 (Th1) and interferon (IFN)-γ-producing CD8<sup>+</sup> T cells. However, N-exo-stimulated DCs induced semi-mature phenotypes and functions, eventually inhibiting T cell proliferation, decreasing IFN-γ, and increasing IL-10-producing CD4<sup>+</sup> T cells. In addition, although N-exo and G-exo stimulations showed similar levels of antigen-specific IFN-γ production, which served as tumor antigen sources in melanoma-specific T cells, G-exo-stimulated DC vaccination conferred a stronger tumor growth inhibition than N-exo-stimulated DC vaccination; further, this was accompanied by a high frequency of tumor-specific, multifunctional effector T cells. These results suggest that gamma irradiation could provide important clues for designing and developing effective exosome vaccines that can induce strong immunogenicity, especially tumor-specific multifunctional T cell responses.https://www.mdpi.com/2076-393X/8/4/699melanoma cancer exosomegamma irradiationdendritic cellstumor antigen-specific multifunctional T cellsvaccine |
| spellingShingle | Woo Sik Kim DaeSeong Choi Ji Min Park Ha-Yeon Song Ho Seong Seo Dong-Eun Lee Eui-Baek Byun Comparison of Exosomes Derived from Non- and Gamma-Irradiated Melanoma Cancer Cells as a Potential Antigenic and Immunogenic Source for Dendritic Cell-Based Immunotherapeutic Vaccine Vaccines melanoma cancer exosome gamma irradiation dendritic cells tumor antigen-specific multifunctional T cells vaccine |
| title | Comparison of Exosomes Derived from Non- and Gamma-Irradiated Melanoma Cancer Cells as a Potential Antigenic and Immunogenic Source for Dendritic Cell-Based Immunotherapeutic Vaccine |
| title_full | Comparison of Exosomes Derived from Non- and Gamma-Irradiated Melanoma Cancer Cells as a Potential Antigenic and Immunogenic Source for Dendritic Cell-Based Immunotherapeutic Vaccine |
| title_fullStr | Comparison of Exosomes Derived from Non- and Gamma-Irradiated Melanoma Cancer Cells as a Potential Antigenic and Immunogenic Source for Dendritic Cell-Based Immunotherapeutic Vaccine |
| title_full_unstemmed | Comparison of Exosomes Derived from Non- and Gamma-Irradiated Melanoma Cancer Cells as a Potential Antigenic and Immunogenic Source for Dendritic Cell-Based Immunotherapeutic Vaccine |
| title_short | Comparison of Exosomes Derived from Non- and Gamma-Irradiated Melanoma Cancer Cells as a Potential Antigenic and Immunogenic Source for Dendritic Cell-Based Immunotherapeutic Vaccine |
| title_sort | comparison of exosomes derived from non and gamma irradiated melanoma cancer cells as a potential antigenic and immunogenic source for dendritic cell based immunotherapeutic vaccine |
| topic | melanoma cancer exosome gamma irradiation dendritic cells tumor antigen-specific multifunctional T cells vaccine |
| url | https://www.mdpi.com/2076-393X/8/4/699 |
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