Decreased melanoma CSF-1 secretion by Cannabigerol treatment reprograms regulatory myeloid cells and reduces tumor progression
During solid tumor progression, the tumor microenvironment (TME) evolves into a highly immunosuppressive milieu. Key players in the immunosuppressive environment are regulatory myeloid cells, including myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs), which are recrui...
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Taylor & Francis Group
2023-12-01
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| Series: | OncoImmunology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2023.2219164 |
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| author | Iris Wyrobnik Miryam Steinberg Anat Gelfand Ronen Rosenblum Yara Eid Mutlak Liron Sulimani Shiri Procaccia Yishai Ofran Hila Novak-Kotzer David Meiri |
| author_facet | Iris Wyrobnik Miryam Steinberg Anat Gelfand Ronen Rosenblum Yara Eid Mutlak Liron Sulimani Shiri Procaccia Yishai Ofran Hila Novak-Kotzer David Meiri |
| author_sort | Iris Wyrobnik |
| collection | DOAJ |
| description | During solid tumor progression, the tumor microenvironment (TME) evolves into a highly immunosuppressive milieu. Key players in the immunosuppressive environment are regulatory myeloid cells, including myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs), which are recruited and activated via tumor-secreted cytokines such as colony-stimulating factor 1 (CSF-1). Therefore, the depletion of tumor-secreted cytokines is a leading anticancer strategy. Here, we found that CSF-1 secretion by melanoma cells is decreased following treatment with Cannabis extracts. Cannabigerol (CBG) was identified as the bioactive cannabinoid responsible for the effects. Conditioned media from cells treated with pure CBG or the high-CBG extract reduced the expansion and macrophage transition of the monocytic-MDSC subpopulation. Treated MO-MDSCs also expressed lower levels of iNOS, leading to restored CD8+ T-cell activation. Tumor-bearing mice treated with CBG presented reduced tumor progression, lower TAM frequencies and reduced TAM/M1 ratio. A combination of CBG and αPD-L1 was more effective in reducing tumor progression, enhancing survival and increasing the infiltration of activated cytotoxic T-cells than each treatment separately. We show a novel mechanism for CBG in modulating the TME and enhancing immune checkpoint blockade therapy, underlining its promising therapeutic potential for the treatment of a variety of tumors with elevated CSF-1 expression. |
| format | Article |
| id | doaj-art-39ec33dd04e2407db267ecc7cf92338a |
| institution | OA Journals |
| issn | 2162-402X |
| language | English |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-39ec33dd04e2407db267ecc7cf92338a2025-08-20T02:01:29ZengTaylor & Francis GroupOncoImmunology2162-402X2023-12-0112110.1080/2162402X.2023.2219164Decreased melanoma CSF-1 secretion by Cannabigerol treatment reprograms regulatory myeloid cells and reduces tumor progressionIris Wyrobnik0Miryam Steinberg1Anat Gelfand2Ronen Rosenblum3Yara Eid Mutlak4Liron Sulimani5Shiri Procaccia6Yishai Ofran7Hila Novak-Kotzer8David Meiri9The Laboratory of Cancer Biology and Cannabinoid Research, Department of Biology, Technion-Israel Institute of Technology, Haifa, IsraelThe Laboratory of Cancer Biology and Cannabinoid Research, Department of Biology, Technion-Israel Institute of Technology, Haifa, IsraelThe Laboratory of Cancer Biology and Cannabinoid Research, Department of Biology, Technion-Israel Institute of Technology, Haifa, IsraelThe Laboratory of Cancer Biology and Cannabinoid Research, Department of Biology, Technion-Israel Institute of Technology, Haifa, IsraelThe Laboratory of Cancer Biology and Cannabinoid Research, Department of Biology, Technion-Israel Institute of Technology, Haifa, IsraelThe Kleifeld Laboratory, Department of Biology, Technion-Israel Institute of Technology, Haifa, IsraelThe Laboratory of Cancer Biology and Cannabinoid Research, Department of Biology, Technion-Israel Institute of Technology, Haifa, IsraelDepartment of Hematology, Shaare Zedek Medical Center and Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, IsraelThe Laboratory of Cancer Biology and Cannabinoid Research, Department of Biology, Technion-Israel Institute of Technology, Haifa, IsraelThe Laboratory of Cancer Biology and Cannabinoid Research, Department of Biology, Technion-Israel Institute of Technology, Haifa, IsraelDuring solid tumor progression, the tumor microenvironment (TME) evolves into a highly immunosuppressive milieu. Key players in the immunosuppressive environment are regulatory myeloid cells, including myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs), which are recruited and activated via tumor-secreted cytokines such as colony-stimulating factor 1 (CSF-1). Therefore, the depletion of tumor-secreted cytokines is a leading anticancer strategy. Here, we found that CSF-1 secretion by melanoma cells is decreased following treatment with Cannabis extracts. Cannabigerol (CBG) was identified as the bioactive cannabinoid responsible for the effects. Conditioned media from cells treated with pure CBG or the high-CBG extract reduced the expansion and macrophage transition of the monocytic-MDSC subpopulation. Treated MO-MDSCs also expressed lower levels of iNOS, leading to restored CD8+ T-cell activation. Tumor-bearing mice treated with CBG presented reduced tumor progression, lower TAM frequencies and reduced TAM/M1 ratio. A combination of CBG and αPD-L1 was more effective in reducing tumor progression, enhancing survival and increasing the infiltration of activated cytotoxic T-cells than each treatment separately. We show a novel mechanism for CBG in modulating the TME and enhancing immune checkpoint blockade therapy, underlining its promising therapeutic potential for the treatment of a variety of tumors with elevated CSF-1 expression.https://www.tandfonline.com/doi/10.1080/2162402X.2023.2219164Tumor MicroenvironmentRegulatory Myeloid CellsCSF-1 (M-CSF)MDSCTAMCannabis |
| spellingShingle | Iris Wyrobnik Miryam Steinberg Anat Gelfand Ronen Rosenblum Yara Eid Mutlak Liron Sulimani Shiri Procaccia Yishai Ofran Hila Novak-Kotzer David Meiri Decreased melanoma CSF-1 secretion by Cannabigerol treatment reprograms regulatory myeloid cells and reduces tumor progression OncoImmunology Tumor Microenvironment Regulatory Myeloid Cells CSF-1 (M-CSF) MDSC TAM Cannabis |
| title | Decreased melanoma CSF-1 secretion by Cannabigerol treatment reprograms regulatory myeloid cells and reduces tumor progression |
| title_full | Decreased melanoma CSF-1 secretion by Cannabigerol treatment reprograms regulatory myeloid cells and reduces tumor progression |
| title_fullStr | Decreased melanoma CSF-1 secretion by Cannabigerol treatment reprograms regulatory myeloid cells and reduces tumor progression |
| title_full_unstemmed | Decreased melanoma CSF-1 secretion by Cannabigerol treatment reprograms regulatory myeloid cells and reduces tumor progression |
| title_short | Decreased melanoma CSF-1 secretion by Cannabigerol treatment reprograms regulatory myeloid cells and reduces tumor progression |
| title_sort | decreased melanoma csf 1 secretion by cannabigerol treatment reprograms regulatory myeloid cells and reduces tumor progression |
| topic | Tumor Microenvironment Regulatory Myeloid Cells CSF-1 (M-CSF) MDSC TAM Cannabis |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2023.2219164 |
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