Extracellular Vesicle-Mediated IL-1 Signaling in Response to Doxorubicin Activates PD-L1 Expression in Osteosarcoma Models
Issued Date
2022-03-01
Resource Type
eISSN
20734409
Scopus ID
2-s2.0-85126590872
Pubmed ID
35326493
Journal Title
Cells
Volume
11
Issue
6
Rights Holder(s)
SCOPUS
Bibliographic Citation
Cells Vol.11 No.6 (2022)
Suggested Citation
Yati S. Extracellular Vesicle-Mediated IL-1 Signaling in Response to Doxorubicin Activates PD-L1 Expression in Osteosarcoma Models. Cells Vol.11 No.6 (2022). doi:10.3390/cells11061042 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/86059
Title
Extracellular Vesicle-Mediated IL-1 Signaling in Response to Doxorubicin Activates PD-L1 Expression in Osteosarcoma Models
Author(s)
Author's Affiliation
Other Contributor(s)
Abstract
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.