Damage-associated molecular patterns (DAMPs) related to immunogenic cell death are differentially triggered by clinically relevant chemotherapeutics in lung adenocarcinoma cells
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRGS |
Texto Completo: | http://hdl.handle.net/10183/212767 |
Resumo: | Background: Chemotherapeutics can stimulate immune antitumor response by inducing immunogenic cell death (ICD), which is activated by Damage-Associated Molecular Patterns (DAMPs) like the exposure of calreticulin (CRT) on the cell surface, the release of ATP and the secretion of High Mobility Group Box 1 (HMGB1). Methods: Here, we investigated the levels of ICD-associated DAMPs induced by chemotherapeutics commonly used in the clinical practice of non-small cell lung cancer (NSCLC) and the association of these DAMPs with apoptosis and autophagy. A549 human lung adenocarcinoma cells were treated with clinically relevant doses of cisplatin, carboplatin, etoposide, paclitaxel and gemcitabine. We assessed ICD-associated DAMPs, cell viability, apoptosis and autophagy in an integrated way. Results: Cisplatin and its combination with etoposide induced the highest levels of apoptosis, while etoposide was the less pro-apoptotic treatment. Cisplatin also induced the highest levels of ICD-associated DAMPs, which was not incremented by co-treatments. Etoposide induced the lower levels of ICD and the highest levels of autophagy, suggesting that the cytoprotective role of autophagy is dominant in relation to its pro-ICD role. High levels of CRT were associated with better prognosis in TCGA databank. In an integrative analysis we found a strong positive correlation between DAMPs and apoptosis, and a negative correlation between cell number and ICD-associated DAMPs as well as between autophagy and apoptosis markers. We also purpose a mathematical integration of ICD-associated DAMPs in an index that may represent with greater biological relevance this process. Cisplatin-treated cells showed the highest IndImmunog, while etoposide was the less immunogenic and the more pro-autophagic treatment. Conclusions: Cisplatin alone induced the highest levels of ICD-associated DAMPs, so that its combination with immunotherapy may be a promising therapeutic strategy in NSCLC. |
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Solari, José Ignácio GonzalezChiela, Eduardo Cremonese FilippiPilar, Emily Ferreira SallesNunes, Vitoria Brum da SilvaGonzalez, Esteban AlbertoFigueiró, FabrícioAndrade, Cristiano FeijóKlamt, Fabio2020-08-08T03:46:20Z20201471-2407http://hdl.handle.net/10183/212767001115071Background: Chemotherapeutics can stimulate immune antitumor response by inducing immunogenic cell death (ICD), which is activated by Damage-Associated Molecular Patterns (DAMPs) like the exposure of calreticulin (CRT) on the cell surface, the release of ATP and the secretion of High Mobility Group Box 1 (HMGB1). Methods: Here, we investigated the levels of ICD-associated DAMPs induced by chemotherapeutics commonly used in the clinical practice of non-small cell lung cancer (NSCLC) and the association of these DAMPs with apoptosis and autophagy. A549 human lung adenocarcinoma cells were treated with clinically relevant doses of cisplatin, carboplatin, etoposide, paclitaxel and gemcitabine. We assessed ICD-associated DAMPs, cell viability, apoptosis and autophagy in an integrated way. Results: Cisplatin and its combination with etoposide induced the highest levels of apoptosis, while etoposide was the less pro-apoptotic treatment. Cisplatin also induced the highest levels of ICD-associated DAMPs, which was not incremented by co-treatments. Etoposide induced the lower levels of ICD and the highest levels of autophagy, suggesting that the cytoprotective role of autophagy is dominant in relation to its pro-ICD role. High levels of CRT were associated with better prognosis in TCGA databank. In an integrative analysis we found a strong positive correlation between DAMPs and apoptosis, and a negative correlation between cell number and ICD-associated DAMPs as well as between autophagy and apoptosis markers. We also purpose a mathematical integration of ICD-associated DAMPs in an index that may represent with greater biological relevance this process. Cisplatin-treated cells showed the highest IndImmunog, while etoposide was the less immunogenic and the more pro-autophagic treatment. Conclusions: Cisplatin alone induced the highest levels of ICD-associated DAMPs, so that its combination with immunotherapy may be a promising therapeutic strategy in NSCLC.application/pdfengBMC cancer. London. Vol. 20, no. 1 (May 2020), 474, 14 p.Adenocarcinoma de pulmãoCarcinoma pulmonar de células não pequenasMorte celularAutofagiaCisplatinoEtoposídeoAutophagyCisplatinDamage-associated molecular patterns (DAMPs)EtoposideImmunogenic cell death (ICD)Non-small cell lung carcinoma (NSCLC)Damage-associated molecular patterns (DAMPs) related to immunogenic cell death are differentially triggered by clinically relevant chemotherapeutics in lung adenocarcinoma cellsEstrangeiroinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRGSinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSTEXT001115071.pdf.txt001115071.pdf.txtExtracted Texttext/plain63554http://www.lume.ufrgs.br/bitstream/10183/212767/2/001115071.pdf.txtee182083a3358d0cbcfc1c72ebcb5b12MD52ORIGINAL001115071.pdfTexto completo (inglês)application/pdf2690747http://www.lume.ufrgs.br/bitstream/10183/212767/1/001115071.pdf4b758556ddf093bef9883515d3968eedMD5110183/2127672020-08-09 03:32:59.505516oai:www.lume.ufrgs.br:10183/212767Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2020-08-09T06:32:59Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false |
dc.title.pt_BR.fl_str_mv |
Damage-associated molecular patterns (DAMPs) related to immunogenic cell death are differentially triggered by clinically relevant chemotherapeutics in lung adenocarcinoma cells |
title |
Damage-associated molecular patterns (DAMPs) related to immunogenic cell death are differentially triggered by clinically relevant chemotherapeutics in lung adenocarcinoma cells |
spellingShingle |
Damage-associated molecular patterns (DAMPs) related to immunogenic cell death are differentially triggered by clinically relevant chemotherapeutics in lung adenocarcinoma cells Solari, José Ignácio Gonzalez Adenocarcinoma de pulmão Carcinoma pulmonar de células não pequenas Morte celular Autofagia Cisplatino Etoposídeo Autophagy Cisplatin Damage-associated molecular patterns (DAMPs) Etoposide Immunogenic cell death (ICD) Non-small cell lung carcinoma (NSCLC) |
title_short |
Damage-associated molecular patterns (DAMPs) related to immunogenic cell death are differentially triggered by clinically relevant chemotherapeutics in lung adenocarcinoma cells |
title_full |
Damage-associated molecular patterns (DAMPs) related to immunogenic cell death are differentially triggered by clinically relevant chemotherapeutics in lung adenocarcinoma cells |
title_fullStr |
Damage-associated molecular patterns (DAMPs) related to immunogenic cell death are differentially triggered by clinically relevant chemotherapeutics in lung adenocarcinoma cells |
title_full_unstemmed |
Damage-associated molecular patterns (DAMPs) related to immunogenic cell death are differentially triggered by clinically relevant chemotherapeutics in lung adenocarcinoma cells |
title_sort |
Damage-associated molecular patterns (DAMPs) related to immunogenic cell death are differentially triggered by clinically relevant chemotherapeutics in lung adenocarcinoma cells |
author |
Solari, José Ignácio Gonzalez |
author_facet |
Solari, José Ignácio Gonzalez Chiela, Eduardo Cremonese Filippi Pilar, Emily Ferreira Salles Nunes, Vitoria Brum da Silva Gonzalez, Esteban Alberto Figueiró, Fabrício Andrade, Cristiano Feijó Klamt, Fabio |
author_role |
author |
author2 |
Chiela, Eduardo Cremonese Filippi Pilar, Emily Ferreira Salles Nunes, Vitoria Brum da Silva Gonzalez, Esteban Alberto Figueiró, Fabrício Andrade, Cristiano Feijó Klamt, Fabio |
author2_role |
author author author author author author author |
dc.contributor.author.fl_str_mv |
Solari, José Ignácio Gonzalez Chiela, Eduardo Cremonese Filippi Pilar, Emily Ferreira Salles Nunes, Vitoria Brum da Silva Gonzalez, Esteban Alberto Figueiró, Fabrício Andrade, Cristiano Feijó Klamt, Fabio |
dc.subject.por.fl_str_mv |
Adenocarcinoma de pulmão Carcinoma pulmonar de células não pequenas Morte celular Autofagia Cisplatino Etoposídeo |
topic |
Adenocarcinoma de pulmão Carcinoma pulmonar de células não pequenas Morte celular Autofagia Cisplatino Etoposídeo Autophagy Cisplatin Damage-associated molecular patterns (DAMPs) Etoposide Immunogenic cell death (ICD) Non-small cell lung carcinoma (NSCLC) |
dc.subject.eng.fl_str_mv |
Autophagy Cisplatin Damage-associated molecular patterns (DAMPs) Etoposide Immunogenic cell death (ICD) Non-small cell lung carcinoma (NSCLC) |
description |
Background: Chemotherapeutics can stimulate immune antitumor response by inducing immunogenic cell death (ICD), which is activated by Damage-Associated Molecular Patterns (DAMPs) like the exposure of calreticulin (CRT) on the cell surface, the release of ATP and the secretion of High Mobility Group Box 1 (HMGB1). Methods: Here, we investigated the levels of ICD-associated DAMPs induced by chemotherapeutics commonly used in the clinical practice of non-small cell lung cancer (NSCLC) and the association of these DAMPs with apoptosis and autophagy. A549 human lung adenocarcinoma cells were treated with clinically relevant doses of cisplatin, carboplatin, etoposide, paclitaxel and gemcitabine. We assessed ICD-associated DAMPs, cell viability, apoptosis and autophagy in an integrated way. Results: Cisplatin and its combination with etoposide induced the highest levels of apoptosis, while etoposide was the less pro-apoptotic treatment. Cisplatin also induced the highest levels of ICD-associated DAMPs, which was not incremented by co-treatments. Etoposide induced the lower levels of ICD and the highest levels of autophagy, suggesting that the cytoprotective role of autophagy is dominant in relation to its pro-ICD role. High levels of CRT were associated with better prognosis in TCGA databank. In an integrative analysis we found a strong positive correlation between DAMPs and apoptosis, and a negative correlation between cell number and ICD-associated DAMPs as well as between autophagy and apoptosis markers. We also purpose a mathematical integration of ICD-associated DAMPs in an index that may represent with greater biological relevance this process. Cisplatin-treated cells showed the highest IndImmunog, while etoposide was the less immunogenic and the more pro-autophagic treatment. Conclusions: Cisplatin alone induced the highest levels of ICD-associated DAMPs, so that its combination with immunotherapy may be a promising therapeutic strategy in NSCLC. |
publishDate |
2020 |
dc.date.accessioned.fl_str_mv |
2020-08-08T03:46:20Z |
dc.date.issued.fl_str_mv |
2020 |
dc.type.driver.fl_str_mv |
Estrangeiro info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
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publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10183/212767 |
dc.identifier.issn.pt_BR.fl_str_mv |
1471-2407 |
dc.identifier.nrb.pt_BR.fl_str_mv |
001115071 |
identifier_str_mv |
1471-2407 001115071 |
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http://hdl.handle.net/10183/212767 |
dc.language.iso.fl_str_mv |
eng |
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eng |
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BMC cancer. London. Vol. 20, no. 1 (May 2020), 474, 14 p. |
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openAccess |
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