Enhancing the efficacy of vaccinia-based oncolytic virotherapy by inhibiting CXCR2-mediated MDSC trafficking
© The Author(s) 2023. Published by Oxford University Press on behalf of Society for Leukocyte Biology. All rights reserved. For permissions, please e-mail: journals.permissionsoup.com..
Oncolytic virotherapy is an innovative approach for cancer treatment. However, recruitment of myeloid-derived suppressor cells (MDSCs) into the tumor microenvironment (TME) after oncolysis-mediated local inflammation leads to tumor resistance to the therapy. Using the murine malignant mesothelioma model, we demonstrated that the in situ vaccinia virotherapy recruited primarily polymorphonuclear MDSCs (PMN-MDSCs) into the TME, where they exhibited strong suppression of cytotoxic T lymphocytes in a reactive oxygen species-dependent way. Single-cell RNA sequencing analysis confirmed the suppressive profile of PMN-MDSCs at the transcriptomic level and identified CXCR2 as a therapeutic target expressed on PMN-MDSCs. Abrogating PMN-MDSC trafficking by CXCR2-specific small molecule inhibitor during the vaccinia virotherapy exhibited enhanced antitumor efficacy in 3 syngeneic cancer models, through increasing CD8+/MDSC ratios in the TME, activating cytotoxic T lymphocytes, and skewing suppressive TME into an antitumor environment. Our results warrant clinical development of CXCR2 inhibitor in combination with oncolytic virotherapy.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:115 |
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| Enthalten in: |
Journal of leukocyte biology - 115(2024), 4 vom: 29. März, Seite 633-646 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Tan, Zhiwu [VerfasserIn] |
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| Links: |
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| Themen: |
CTL |
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| Anmerkungen: |
Date Completed 01.04.2024 Date Revised 02.04.2024 published: Print Citation Status MEDLINE |
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| doi: |
10.1093/jleuko/qiad150 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a © The Author(s) 2023. Published by Oxford University Press on behalf of Society for Leukocyte Biology. All rights reserved. For permissions, please e-mail: journals.permissionsoup.com. | ||
| 520 | |a Oncolytic virotherapy is an innovative approach for cancer treatment. However, recruitment of myeloid-derived suppressor cells (MDSCs) into the tumor microenvironment (TME) after oncolysis-mediated local inflammation leads to tumor resistance to the therapy. Using the murine malignant mesothelioma model, we demonstrated that the in situ vaccinia virotherapy recruited primarily polymorphonuclear MDSCs (PMN-MDSCs) into the TME, where they exhibited strong suppression of cytotoxic T lymphocytes in a reactive oxygen species-dependent way. Single-cell RNA sequencing analysis confirmed the suppressive profile of PMN-MDSCs at the transcriptomic level and identified CXCR2 as a therapeutic target expressed on PMN-MDSCs. Abrogating PMN-MDSC trafficking by CXCR2-specific small molecule inhibitor during the vaccinia virotherapy exhibited enhanced antitumor efficacy in 3 syngeneic cancer models, through increasing CD8+/MDSC ratios in the TME, activating cytotoxic T lymphocytes, and skewing suppressive TME into an antitumor environment. Our results warrant clinical development of CXCR2 inhibitor in combination with oncolytic virotherapy | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a CTL | |
| 650 | 4 | |a CXCR2 | |
| 650 | 4 | |a MDSC | |
| 650 | 4 | |a cancer immunotherapy | |
| 650 | 4 | |a immunosuppression | |
| 650 | 4 | |a inflammation | |
| 650 | 4 | |a oncolytic virotherapy | |
| 650 | 4 | |a vaccinia virus | |
| 700 | 1 | |a Chiu, Mei Sum |e verfasserin |4 aut | |
| 700 | 1 | |a Yue, Ming |e verfasserin |4 aut | |
| 700 | 1 | |a Kwok, Hau Yee |e verfasserin |4 aut | |
| 700 | 1 | |a Tse, Man Ho |e verfasserin |4 aut | |
| 700 | 1 | |a Wen, Yang |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Bohao |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Dawei |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Dongyan |e verfasserin |4 aut | |
| 700 | 1 | |a Song, You-Qiang |e verfasserin |4 aut | |
| 700 | 1 | |a Man, Kwan |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Zhiwei |e verfasserin |4 aut | |
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