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Extracellular Vesicle-Mediated IL-1 Signaling in Response to Doxorubicin Activates PD-L1 Expression in Osteosarcoma Models
The expression of programmed cell death ligand 1 (PD-L1) in tumors is associated with tumor cell escape from T-cell cytotoxicity, and is considered a crucial effector in chemoresistance and tumor relapse. Although PD-L1 induction has been observed in patients after chemotherapy treatment, the mechan...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8946890/ https://www.ncbi.nlm.nih.gov/pubmed/35326493 http://dx.doi.org/10.3390/cells11061042 |
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author | Yati, Su Silathapanasakul, Atiruj Thakaeng, Chakrarin Chanasakulniyom, Mayuree Songtawee, Napat Porntadavity, Sureerut Pothacharoen, Peraphan Pruksakorn, Dumnoensun Kongtawelert, Prachya Yenchitsomanus, Pa-thai Chanmee, Theerawut |
author_facet | Yati, Su Silathapanasakul, Atiruj Thakaeng, Chakrarin Chanasakulniyom, Mayuree Songtawee, Napat Porntadavity, Sureerut Pothacharoen, Peraphan Pruksakorn, Dumnoensun Kongtawelert, Prachya Yenchitsomanus, Pa-thai Chanmee, Theerawut |
author_sort | Yati, Su |
collection | PubMed |
description | The expression of programmed cell death ligand 1 (PD-L1) in tumors is associated with tumor cell escape from T-cell cytotoxicity, and is considered a crucial effector in chemoresistance and tumor relapse. Although PD-L1 induction has been observed in patients after chemotherapy treatment, the mechanism by which the drug activates PD-L1 expression remains elusive. Here, we identified the extracellular vesicles (EVs) as a molecular mediator that determines the effect of doxorubicin on PD-L1 expression in osteosarcoma models. Mechanistically, doxorubicin dependently stimulates the release of extracellular vesicles, which mediate autocrine/paracrine signals in osteosarcoma cells. The recipient cells were stimulated by these EVs and acquired the ability to promote the expression of inflammatory cytokines interleukin (IL)-1β and IL-6. In response to doxorubicin, IL-1β, but not IL-6, allowed- osteosarcoma cells to promote the expression of PD-L1, and the elimination of IL-1β/IL-1 receptor signaling with IL-1 receptor antagonist reduced PD-L1 expression. Together, these findings provided insights into the role of EV release in response to chemotherapy that mediates PD-L1 expression via the IL-1 signaling pathway, and suggested that the combination of a drug targeting IL-1 or PD-L1 with chemotherapy could be an effective treatment option for osteosarcoma patients. |
format | Online Article Text |
id | pubmed-8946890 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-89468902022-03-25 Extracellular Vesicle-Mediated IL-1 Signaling in Response to Doxorubicin Activates PD-L1 Expression in Osteosarcoma Models Yati, Su Silathapanasakul, Atiruj Thakaeng, Chakrarin Chanasakulniyom, Mayuree Songtawee, Napat Porntadavity, Sureerut Pothacharoen, Peraphan Pruksakorn, Dumnoensun Kongtawelert, Prachya Yenchitsomanus, Pa-thai Chanmee, Theerawut Cells Article The expression of programmed cell death ligand 1 (PD-L1) in tumors is associated with tumor cell escape from T-cell cytotoxicity, and is considered a crucial effector in chemoresistance and tumor relapse. Although PD-L1 induction has been observed in patients after chemotherapy treatment, the mechanism by which the drug activates PD-L1 expression remains elusive. Here, we identified the extracellular vesicles (EVs) as a molecular mediator that determines the effect of doxorubicin on PD-L1 expression in osteosarcoma models. Mechanistically, doxorubicin dependently stimulates the release of extracellular vesicles, which mediate autocrine/paracrine signals in osteosarcoma cells. The recipient cells were stimulated by these EVs and acquired the ability to promote the expression of inflammatory cytokines interleukin (IL)-1β and IL-6. In response to doxorubicin, IL-1β, but not IL-6, allowed- osteosarcoma cells to promote the expression of PD-L1, and the elimination of IL-1β/IL-1 receptor signaling with IL-1 receptor antagonist reduced PD-L1 expression. Together, these findings provided insights into the role of EV release in response to chemotherapy that mediates PD-L1 expression via the IL-1 signaling pathway, and suggested that the combination of a drug targeting IL-1 or PD-L1 with chemotherapy could be an effective treatment option for osteosarcoma patients. MDPI 2022-03-18 /pmc/articles/PMC8946890/ /pubmed/35326493 http://dx.doi.org/10.3390/cells11061042 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Yati, Su Silathapanasakul, Atiruj Thakaeng, Chakrarin Chanasakulniyom, Mayuree Songtawee, Napat Porntadavity, Sureerut Pothacharoen, Peraphan Pruksakorn, Dumnoensun Kongtawelert, Prachya Yenchitsomanus, Pa-thai Chanmee, Theerawut Extracellular Vesicle-Mediated IL-1 Signaling in Response to Doxorubicin Activates PD-L1 Expression in Osteosarcoma Models |
title | Extracellular Vesicle-Mediated IL-1 Signaling in Response to Doxorubicin Activates PD-L1 Expression in Osteosarcoma Models |
title_full | Extracellular Vesicle-Mediated IL-1 Signaling in Response to Doxorubicin Activates PD-L1 Expression in Osteosarcoma Models |
title_fullStr | Extracellular Vesicle-Mediated IL-1 Signaling in Response to Doxorubicin Activates PD-L1 Expression in Osteosarcoma Models |
title_full_unstemmed | Extracellular Vesicle-Mediated IL-1 Signaling in Response to Doxorubicin Activates PD-L1 Expression in Osteosarcoma Models |
title_short | Extracellular Vesicle-Mediated IL-1 Signaling in Response to Doxorubicin Activates PD-L1 Expression in Osteosarcoma Models |
title_sort | extracellular vesicle-mediated il-1 signaling in response to doxorubicin activates pd-l1 expression in osteosarcoma models |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8946890/ https://www.ncbi.nlm.nih.gov/pubmed/35326493 http://dx.doi.org/10.3390/cells11061042 |
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