Myeloma-derived IL-32γ induced PD-L1 expression in macrophages facilitates immune escape via the PFKFB3-JAK1 axis
Multiple myeloma (MM) is characterized by an accumulation of monoclonal plasma cells within the bone marrow (BM). Macrophages are an abundant component of myeloma BM microenvironment and support survival of the malignant cells and foster myeloma development and progression by suppression of the immu...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | OncoImmunology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2022.2057837 |
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| author | Yang Liu Haimeng Yan Huiyao Gu Enfan Zhang Jingsong He Wen Cao Jianwei Qu Ruyi Xu Liqin Cao Donghua He Jinna Zhang Yifan Hou Zhen Cai |
| author_facet | Yang Liu Haimeng Yan Huiyao Gu Enfan Zhang Jingsong He Wen Cao Jianwei Qu Ruyi Xu Liqin Cao Donghua He Jinna Zhang Yifan Hou Zhen Cai |
| author_sort | Yang Liu |
| collection | DOAJ |
| description | Multiple myeloma (MM) is characterized by an accumulation of monoclonal plasma cells within the bone marrow (BM). Macrophages are an abundant component of myeloma BM microenvironment and support survival of the malignant cells and foster myeloma development and progression by suppression of the immune response. In our previous study, we found that MM patients overexpress pro-inflammatory cytokine interleukin-32 (IL-32). The present study aimed to investigate the role of IL-32 in myeloma progression and mechanisms of IL-32 on macrophages functions. We discovered that the expression of IL-32 was associated with the disease stage in myeloma patients. MM-derived exosomes containing IL-32γ promoted the expression of programmed death-ligand 1(PD-L1) by macrophages, thus promoting immune evasion. Mechanistically, myeloma-secreted IL-32γ acted via proteinase 3 (PR3) to enhance 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) dependent glycolysis and subsequent PD-L1 expression. Moreover, the PFKFB3-Janus kinase 1 (JAK1) axis might contribute to the expression of PD-L1 by macrophages. To sum up, we concluded that IL-32 was a critical mediator in myeloma progression, and targeting IL-32 signaling might be used as a potential strategy for treating myeloma. |
| first_indexed | 2024-12-13T22:20:08Z |
| format | Article |
| id | doaj.art-3096814808fa48bd96eb3ccae14178d0 |
| institution | Directory Open Access Journal |
| issn | 2162-402X |
| language | English |
| last_indexed | 2024-12-13T22:20:08Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj.art-3096814808fa48bd96eb3ccae14178d02022-12-21T23:29:23ZengTaylor & Francis GroupOncoImmunology2162-402X2022-12-0111110.1080/2162402X.2022.2057837Myeloma-derived IL-32γ induced PD-L1 expression in macrophages facilitates immune escape via the PFKFB3-JAK1 axisYang Liu0Haimeng Yan1Huiyao Gu2Enfan Zhang3Jingsong He4Wen Cao5Jianwei Qu6Ruyi Xu7Liqin Cao8Donghua He9Jinna Zhang10Yifan Hou11Zhen Cai12Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, ChinaBone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, ChinaBone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, ChinaBone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, ChinaBone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, ChinaBone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, ChinaBone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, ChinaBone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, ChinaBone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, ChinaBone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, ChinaBone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, ChinaBone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, ChinaBone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, ChinaMultiple myeloma (MM) is characterized by an accumulation of monoclonal plasma cells within the bone marrow (BM). Macrophages are an abundant component of myeloma BM microenvironment and support survival of the malignant cells and foster myeloma development and progression by suppression of the immune response. In our previous study, we found that MM patients overexpress pro-inflammatory cytokine interleukin-32 (IL-32). The present study aimed to investigate the role of IL-32 in myeloma progression and mechanisms of IL-32 on macrophages functions. We discovered that the expression of IL-32 was associated with the disease stage in myeloma patients. MM-derived exosomes containing IL-32γ promoted the expression of programmed death-ligand 1(PD-L1) by macrophages, thus promoting immune evasion. Mechanistically, myeloma-secreted IL-32γ acted via proteinase 3 (PR3) to enhance 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) dependent glycolysis and subsequent PD-L1 expression. Moreover, the PFKFB3-Janus kinase 1 (JAK1) axis might contribute to the expression of PD-L1 by macrophages. To sum up, we concluded that IL-32 was a critical mediator in myeloma progression, and targeting IL-32 signaling might be used as a potential strategy for treating myeloma.https://www.tandfonline.com/doi/10.1080/2162402X.2022.2057837Multiple myelomaIL-32macrophageglycolysisimmune checkpoint |
| spellingShingle | Yang Liu Haimeng Yan Huiyao Gu Enfan Zhang Jingsong He Wen Cao Jianwei Qu Ruyi Xu Liqin Cao Donghua He Jinna Zhang Yifan Hou Zhen Cai Myeloma-derived IL-32γ induced PD-L1 expression in macrophages facilitates immune escape via the PFKFB3-JAK1 axis OncoImmunology Multiple myeloma IL-32 macrophage glycolysis immune checkpoint |
| title | Myeloma-derived IL-32γ induced PD-L1 expression in macrophages facilitates immune escape via the PFKFB3-JAK1 axis |
| title_full | Myeloma-derived IL-32γ induced PD-L1 expression in macrophages facilitates immune escape via the PFKFB3-JAK1 axis |
| title_fullStr | Myeloma-derived IL-32γ induced PD-L1 expression in macrophages facilitates immune escape via the PFKFB3-JAK1 axis |
| title_full_unstemmed | Myeloma-derived IL-32γ induced PD-L1 expression in macrophages facilitates immune escape via the PFKFB3-JAK1 axis |
| title_short | Myeloma-derived IL-32γ induced PD-L1 expression in macrophages facilitates immune escape via the PFKFB3-JAK1 axis |
| title_sort | myeloma derived il 32γ induced pd l1 expression in macrophages facilitates immune escape via the pfkfb3 jak1 axis |
| topic | Multiple myeloma IL-32 macrophage glycolysis immune checkpoint |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2022.2057837 |
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