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...
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th-mahidol.747302022-08-04T11:28:01Z Extracellular Vesicle-Mediated IL-1 Signaling in Response to Doxorubicin Activates PD-L1 Expression in Osteosarcoma Models Su Yati Atiruj Silathapanasakul Chakrarin Thakaeng Mayuree Chanasakulniyom Napat Songtawee Sureerut Porntadavity Peraphan Pothacharoen Dumnoensun Pruksakorn Prachya Kongtawelert Pa Thai Yenchitsomanus Theerawut Chanmee Siriraj Hospital Faculty of Medicine, Chiang Mai University Mahidol University Medicine 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 dox-orubicin on PD-L1 expression in osteosarcoma models. Mechanistically, doxorubicin dependently stimulates the release of extracellular vesicles, which mediate autocrine/paracrine signals in osteo-sarcoma 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 elimi-nation of IL-1β/IL-1 receptor signaling with IL-1 receptor antagonist reduced PD-L1 expression. To-gether, 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 oste-osarcoma patients. 2022-08-04T04:28:01Z 2022-08-04T04:28:01Z 2022-03-01 Article Cells. Vol.11, No.6 (2022) 10.3390/cells11061042 20734409 2-s2.0-85126590872 https://repository.li.mahidol.ac.th/handle/123456789/74730 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85126590872&origin=inward |
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Medicine Su Yati Atiruj Silathapanasakul Chakrarin Thakaeng Mayuree Chanasakulniyom Napat Songtawee Sureerut Porntadavity Peraphan Pothacharoen Dumnoensun Pruksakorn Prachya Kongtawelert Pa Thai Yenchitsomanus Theerawut Chanmee Extracellular Vesicle-Mediated IL-1 Signaling in Response to Doxorubicin Activates PD-L1 Expression in Osteosarcoma Models |
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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 dox-orubicin on PD-L1 expression in osteosarcoma models. Mechanistically, doxorubicin dependently stimulates the release of extracellular vesicles, which mediate autocrine/paracrine signals in osteo-sarcoma 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 elimi-nation of IL-1β/IL-1 receptor signaling with IL-1 receptor antagonist reduced PD-L1 expression. To-gether, 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 oste-osarcoma patients. |
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Siriraj Hospital |
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Siriraj Hospital Su Yati Atiruj Silathapanasakul Chakrarin Thakaeng Mayuree Chanasakulniyom Napat Songtawee Sureerut Porntadavity Peraphan Pothacharoen Dumnoensun Pruksakorn Prachya Kongtawelert Pa Thai Yenchitsomanus Theerawut Chanmee |
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Su Yati Atiruj Silathapanasakul Chakrarin Thakaeng Mayuree Chanasakulniyom Napat Songtawee Sureerut Porntadavity Peraphan Pothacharoen Dumnoensun Pruksakorn Prachya Kongtawelert Pa Thai Yenchitsomanus Theerawut Chanmee |
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Su Yati |
title |
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_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_sort |
extracellular vesicle-mediated il-1 signaling in response to doxorubicin activates pd-l1 expression in osteosarcoma models |
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2022 |
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https://repository.li.mahidol.ac.th/handle/123456789/74730 |
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1763495923508314112 |