Proteomic Identification of Heat Shock-Induced Danger Signals in a Melanoma Cell Lysate Used in Dendritic Cell-Based Cancer Immunotherapy
Autologous dendritic cells (DCs) loaded with cancer cell-derived lysates have become a promising tool in cancer immunotherapy. During the last decade, we demonstrated that vaccination of advanced melanoma patients with autologous tumor antigen presenting cells (TAPCells) loaded with an allogeneic he...
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| Format: | Article |
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2018-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2018/3982942 |
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| author | Fermín E. González Alexey Chernobrovkin Cristián Pereda Tamara García-Salum Andrés Tittarelli Mercedes N. López Flavio Salazar-Onfray Roman A. Zubarev |
| author_facet | Fermín E. González Alexey Chernobrovkin Cristián Pereda Tamara García-Salum Andrés Tittarelli Mercedes N. López Flavio Salazar-Onfray Roman A. Zubarev |
| author_sort | Fermín E. González |
| collection | DOAJ |
| description | Autologous dendritic cells (DCs) loaded with cancer cell-derived lysates have become a promising tool in cancer immunotherapy. During the last decade, we demonstrated that vaccination of advanced melanoma patients with autologous tumor antigen presenting cells (TAPCells) loaded with an allogeneic heat shock- (HS-) conditioned melanoma cell-derived lysate (called TRIMEL) is able to induce an antitumor immune response associated with a prolonged patient survival. TRIMEL provides not only a broad spectrum of potential melanoma-associated antigens but also danger signals that are crucial in the induction of a committed mature DC phenotype. However, potential changes induced by heat conditioning on the proteome of TRIMEL are still unknown. The identification of newly or differentially expressed proteins under defined stress conditions is relevant for understanding the lysate immunogenicity. Here, we characterized the proteomic profile of TRIMEL in response to HS treatment. A quantitative label-free proteome analysis of over 2800 proteins was performed, with 91 proteins that were found to be regulated by HS treatment: 18 proteins were overexpressed and 73 underexpressed. Additionally, 32 proteins were only identified in the HS-treated TRIMEL and 26 in non HS-conditioned samples. One protein from the overexpressed group and two proteins from the HS-exclusive group were previously described as potential damage-associated molecular patterns (DAMPs). Some of the HS-induced proteins, such as haptoglobin, could be also considered as DAMPs and candidates for further immunological analysis in the establishment of new putative danger signals with immunostimulatory functions. |
| format | Article |
| id | doaj-art-ef1825395fd746dcb5cfe14ad9714aa3 |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-ef1825395fd746dcb5cfe14ad9714aa32025-02-03T05:58:47ZengWileyJournal of Immunology Research2314-88612314-71562018-01-01201810.1155/2018/39829423982942Proteomic Identification of Heat Shock-Induced Danger Signals in a Melanoma Cell Lysate Used in Dendritic Cell-Based Cancer ImmunotherapyFermín E. González0Alexey Chernobrovkin1Cristián Pereda2Tamara García-Salum3Andrés Tittarelli4Mercedes N. López5Flavio Salazar-Onfray6Roman A. Zubarev7Laboratory of Experimental Immunology & Cancer, Faculty of Dentistry, Universidad de Chile, 8380492 Santiago, ChileDepartment of Medical Biochemistry and Biophysics, Karolinska Institute, 17177 Stockholm, SwedenMillennium Institute on Immunology and Immunotherapy, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, 8380453 Santiago, ChileLaboratory of Molecular Virology, Departamento de Enfermedades Infecciosas e Inmunología Pediátrica, School of Medicine, Pontificia Universidad Católica de Chile, 8331150 Santiago, ChileMillennium Institute on Immunology and Immunotherapy, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, 8380453 Santiago, ChileMillennium Institute on Immunology and Immunotherapy, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, 8380453 Santiago, ChileMillennium Institute on Immunology and Immunotherapy, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, 8380453 Santiago, ChileDepartment of Medical Biochemistry and Biophysics, Karolinska Institute, 17177 Stockholm, SwedenAutologous dendritic cells (DCs) loaded with cancer cell-derived lysates have become a promising tool in cancer immunotherapy. During the last decade, we demonstrated that vaccination of advanced melanoma patients with autologous tumor antigen presenting cells (TAPCells) loaded with an allogeneic heat shock- (HS-) conditioned melanoma cell-derived lysate (called TRIMEL) is able to induce an antitumor immune response associated with a prolonged patient survival. TRIMEL provides not only a broad spectrum of potential melanoma-associated antigens but also danger signals that are crucial in the induction of a committed mature DC phenotype. However, potential changes induced by heat conditioning on the proteome of TRIMEL are still unknown. The identification of newly or differentially expressed proteins under defined stress conditions is relevant for understanding the lysate immunogenicity. Here, we characterized the proteomic profile of TRIMEL in response to HS treatment. A quantitative label-free proteome analysis of over 2800 proteins was performed, with 91 proteins that were found to be regulated by HS treatment: 18 proteins were overexpressed and 73 underexpressed. Additionally, 32 proteins were only identified in the HS-treated TRIMEL and 26 in non HS-conditioned samples. One protein from the overexpressed group and two proteins from the HS-exclusive group were previously described as potential damage-associated molecular patterns (DAMPs). Some of the HS-induced proteins, such as haptoglobin, could be also considered as DAMPs and candidates for further immunological analysis in the establishment of new putative danger signals with immunostimulatory functions.http://dx.doi.org/10.1155/2018/3982942 |
| spellingShingle | Fermín E. González Alexey Chernobrovkin Cristián Pereda Tamara García-Salum Andrés Tittarelli Mercedes N. López Flavio Salazar-Onfray Roman A. Zubarev Proteomic Identification of Heat Shock-Induced Danger Signals in a Melanoma Cell Lysate Used in Dendritic Cell-Based Cancer Immunotherapy Journal of Immunology Research |
| title | Proteomic Identification of Heat Shock-Induced Danger Signals in a Melanoma Cell Lysate Used in Dendritic Cell-Based Cancer Immunotherapy |
| title_full | Proteomic Identification of Heat Shock-Induced Danger Signals in a Melanoma Cell Lysate Used in Dendritic Cell-Based Cancer Immunotherapy |
| title_fullStr | Proteomic Identification of Heat Shock-Induced Danger Signals in a Melanoma Cell Lysate Used in Dendritic Cell-Based Cancer Immunotherapy |
| title_full_unstemmed | Proteomic Identification of Heat Shock-Induced Danger Signals in a Melanoma Cell Lysate Used in Dendritic Cell-Based Cancer Immunotherapy |
| title_short | Proteomic Identification of Heat Shock-Induced Danger Signals in a Melanoma Cell Lysate Used in Dendritic Cell-Based Cancer Immunotherapy |
| title_sort | proteomic identification of heat shock induced danger signals in a melanoma cell lysate used in dendritic cell based cancer immunotherapy |
| url | http://dx.doi.org/10.1155/2018/3982942 |
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