Proteomic identification of heat shock induced danger signals in a melanoma cell lysate used in dendritic cell based cancer immunotherapy
Author
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González, Fermin E.
Author
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Chernobrovkin, Alexey
Author
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Pereda, Cristián
Author
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García Salum, Tamara
Author
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López, Mercedes N.
Author
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Salazar Onfray, Flavio
Author
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Zubarev, Roman A.
Author
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Tittarelli, Andrés
Admission date
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2018-07-24T14:23:32Z
Available date
dc.date.available
2018-07-24T14:23:32Z
Publication date
dc.date.issued
2018
Cita de ítem
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Journal of Immunology Research
Volume 2018, Article ID 3982942, 15 pages
es_ES
Identifier
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10.1155/2018/3982942
Identifier
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https://repositorio.uchile.cl/handle/2250/150199
Abstract
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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.
es_ES
Patrocinador
dc.description.sponsorship
Chilean National Fund for Scientific and Technological Development
FONDECYT 11130607
FONDEF ID16I10148
FONDECYT 1171213