Combined Photosensitization and Vaccination Enable CD8 T-Cell Immunity and Tumor Suppression Independent of CD4 T-Cell Help
Cytotoxic T lymphocytes (CTLs) are key players in fighting cancer, and their induction is a major focus in the design of therapeutic vaccines. Yet, therapeutic vaccine efficacy is limited, in part due to the suboptimal vaccine processing by antigen-presenting cells (APCs). Such processing typically...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.01548/full |
| _version_ | 1818148839080591360 |
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| author | Eleni Maria Varypataki Fabio Hasler Ying Waeckerle-Men Sarah Vogel-Kindgen Anders Høgset Thomas M. Kündig Thomas M. Kündig Bruno Gander Cornelia Halin Pål Johansen Pål Johansen |
| author_facet | Eleni Maria Varypataki Fabio Hasler Ying Waeckerle-Men Sarah Vogel-Kindgen Anders Høgset Thomas M. Kündig Thomas M. Kündig Bruno Gander Cornelia Halin Pål Johansen Pål Johansen |
| author_sort | Eleni Maria Varypataki |
| collection | DOAJ |
| description | Cytotoxic T lymphocytes (CTLs) are key players in fighting cancer, and their induction is a major focus in the design of therapeutic vaccines. Yet, therapeutic vaccine efficacy is limited, in part due to the suboptimal vaccine processing by antigen-presenting cells (APCs). Such processing typically takes place via the MHC class II pathway for CD4 T-cell activation and MHC class I pathway for activation of CD8 CTLs. We show that a combination of skin photochemical treatment and immunization, so-called photochemical internalization (PCI) facilitated CTL activation due to the photochemical adjuvant effect induced by photosensitizer, oxygen, and light. Mice were immunized intradermally with antigen and photosensitizer, followed by controlled light exposure. PCI-treated mice showed strong activation of CD8 T cells, with improved IFN-γ production and cytotoxicity, as compared to mice immunized without parallel PCI treatment. Surprisingly, the CD8 T-cell effector functions were not impaired in MHC class II- or CD4 T-cell-deficient mice. Moreover, PCI-based vaccination caused tumor regression independent of MHC class II or CD4 T cells presence in melanoma bearing mice. Together, the data demonstrate that PCI can act as a powerful adjuvant in cancer vaccines, even in hosts with impaired T-helper functions. |
| first_indexed | 2024-12-11T12:57:31Z |
| format | Article |
| id | doaj.art-c0096178e37541498f79e584f063610e |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T12:57:31Z |
| publishDate | 2019-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-c0096178e37541498f79e584f063610e2022-12-22T01:06:32ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-07-011010.3389/fimmu.2019.01548465928Combined Photosensitization and Vaccination Enable CD8 T-Cell Immunity and Tumor Suppression Independent of CD4 T-Cell HelpEleni Maria Varypataki0Fabio Hasler1Ying Waeckerle-Men2Sarah Vogel-Kindgen3Anders Høgset4Thomas M. Kündig5Thomas M. Kündig6Bruno Gander7Cornelia Halin8Pål Johansen9Pål Johansen10Department of Dermatology, University of Zurich, Zurich, SwitzerlandDepartment of Dermatology, University of Zurich, Zurich, SwitzerlandDepartment of Dermatology, University of Zurich, Zurich, SwitzerlandInstitute of Pharmaceutical Sciences, ETH Zurich, Zurich, SwitzerlandPCI Biotech AS, Oslo, NorwayDepartment of Dermatology, University of Zurich, Zurich, SwitzerlandDepartment of Dermatology, University Hospital Zurich, Zurich, SwitzerlandInstitute of Pharmaceutical Sciences, ETH Zurich, Zurich, SwitzerlandInstitute of Pharmaceutical Sciences, ETH Zurich, Zurich, SwitzerlandDepartment of Dermatology, University of Zurich, Zurich, SwitzerlandDepartment of Dermatology, University Hospital Zurich, Zurich, SwitzerlandCytotoxic T lymphocytes (CTLs) are key players in fighting cancer, and their induction is a major focus in the design of therapeutic vaccines. Yet, therapeutic vaccine efficacy is limited, in part due to the suboptimal vaccine processing by antigen-presenting cells (APCs). Such processing typically takes place via the MHC class II pathway for CD4 T-cell activation and MHC class I pathway for activation of CD8 CTLs. We show that a combination of skin photochemical treatment and immunization, so-called photochemical internalization (PCI) facilitated CTL activation due to the photochemical adjuvant effect induced by photosensitizer, oxygen, and light. Mice were immunized intradermally with antigen and photosensitizer, followed by controlled light exposure. PCI-treated mice showed strong activation of CD8 T cells, with improved IFN-γ production and cytotoxicity, as compared to mice immunized without parallel PCI treatment. Surprisingly, the CD8 T-cell effector functions were not impaired in MHC class II- or CD4 T-cell-deficient mice. Moreover, PCI-based vaccination caused tumor regression independent of MHC class II or CD4 T cells presence in melanoma bearing mice. Together, the data demonstrate that PCI can act as a powerful adjuvant in cancer vaccines, even in hosts with impaired T-helper functions.https://www.frontiersin.org/article/10.3389/fimmu.2019.01548/fullvaccinephotochemical internalizationcancer immunotherapymelanomacytotoxic T cellsT-helper cells |
| spellingShingle | Eleni Maria Varypataki Fabio Hasler Ying Waeckerle-Men Sarah Vogel-Kindgen Anders Høgset Thomas M. Kündig Thomas M. Kündig Bruno Gander Cornelia Halin Pål Johansen Pål Johansen Combined Photosensitization and Vaccination Enable CD8 T-Cell Immunity and Tumor Suppression Independent of CD4 T-Cell Help Frontiers in Immunology vaccine photochemical internalization cancer immunotherapy melanoma cytotoxic T cells T-helper cells |
| title | Combined Photosensitization and Vaccination Enable CD8 T-Cell Immunity and Tumor Suppression Independent of CD4 T-Cell Help |
| title_full | Combined Photosensitization and Vaccination Enable CD8 T-Cell Immunity and Tumor Suppression Independent of CD4 T-Cell Help |
| title_fullStr | Combined Photosensitization and Vaccination Enable CD8 T-Cell Immunity and Tumor Suppression Independent of CD4 T-Cell Help |
| title_full_unstemmed | Combined Photosensitization and Vaccination Enable CD8 T-Cell Immunity and Tumor Suppression Independent of CD4 T-Cell Help |
| title_short | Combined Photosensitization and Vaccination Enable CD8 T-Cell Immunity and Tumor Suppression Independent of CD4 T-Cell Help |
| title_sort | combined photosensitization and vaccination enable cd8 t cell immunity and tumor suppression independent of cd4 t cell help |
| topic | vaccine photochemical internalization cancer immunotherapy melanoma cytotoxic T cells T-helper cells |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.01548/full |
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