Interaction between PD-L1 and soluble VEGFR1 in glioblastoma-educated macrophages
Abstract Purpose The combined application of immune checkpoint inhibitors (ICIs) and anti-angiogenesis therapy has shown synergistic effects on glioblastoma (GBM). As important resources of PD-L1 in the tumor microenvironment (TME), tumor-associated macrophages (TAMs) have significant impact of the...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-03-01
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| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12885-023-10733-5 |
| _version_ | 1797864409013420032 |
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| author | Xin Liu Zhenke Li Jinxing Sun Zhijie Zhang Weiguo Li |
| author_facet | Xin Liu Zhenke Li Jinxing Sun Zhijie Zhang Weiguo Li |
| author_sort | Xin Liu |
| collection | DOAJ |
| description | Abstract Purpose The combined application of immune checkpoint inhibitors (ICIs) and anti-angiogenesis therapy has shown synergistic effects on glioblastoma (GBM). As important resources of PD-L1 in the tumor microenvironment (TME), tumor-associated macrophages (TAMs) have significant impact of the efficiency of ICIs. However, the effects of anti-angiogenesis agents on immune checkpoints expression are not fully understood. Method GBM-educated macrophages were generated from circulating monocytes of healthy controls and GBM patients under the education of GBM cell line. Surface expression of PD-L1 and VEGFR1 on GBM-educated macrophages was analyzed. VEGFR1 NAb and soluble VEGFR1 (sVEGFR1) were added and their effects on PD-L1 expression on TAMs was investigated. Serum soluble PD-L1 (sPD-L1) and sVEGFR1 levels in GBM patients were measured and their correlation was analyzed. Result The expression intensity of PD-L1 on GBM-educated macrophages was higher and its up-regulation partially depends on VEGFR1 signaling pathway. GBM-educated macrophages secreted less levels of soluble VEGFR1 (sVEGFR1), and exogenous sVEGFR1 down-regulated PD-L1 expression intensity. PD-L1 blockade promoted the secretion of sVEGFR1. Finally, sVEGFR1 and sPD-L1 in serum of GBM patients were overexpressed, and a positive correlation was found. Conclusion These findings reveal the interaction between PD-L1 and VEGFR1 signaling pathway in GBM-educated macrophages. VEGFR1 is involved with PD-L1 overexpression, which can be impeded by autocrine regulation of sVEGFR1. sVEGFR1 secretion by GBM-educated macrophages can be promoted by PD-L1 blockade. Taken together, these findings provide evidences for the combined application of ICIs and anti-angiogenesis therapies in the treatment of GBM. |
| first_indexed | 2024-04-09T22:51:19Z |
| format | Article |
| id | doaj.art-2a248d3e7c9a4e3d8972ed6b1ccb6238 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-09T22:51:19Z |
| publishDate | 2023-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-2a248d3e7c9a4e3d8972ed6b1ccb62382023-03-22T11:35:09ZengBMCBMC Cancer1471-24072023-03-0123111110.1186/s12885-023-10733-5Interaction between PD-L1 and soluble VEGFR1 in glioblastoma-educated macrophagesXin Liu0Zhenke Li1Jinxing Sun2Zhijie Zhang3Weiguo Li4Department of Ultrasound, Qilu Hospital of Shandong UniversityDepartment of Neurosurgery, Qilu Hospital of Shandong UniversityDepartment of Neurosurgery, Qilu Hospital of Shandong UniversityDepartment of Ultrasound, Shandong Maternal and Child Health HospitalDepartment of Neurosurgery, Qilu Hospital of Shandong UniversityAbstract Purpose The combined application of immune checkpoint inhibitors (ICIs) and anti-angiogenesis therapy has shown synergistic effects on glioblastoma (GBM). As important resources of PD-L1 in the tumor microenvironment (TME), tumor-associated macrophages (TAMs) have significant impact of the efficiency of ICIs. However, the effects of anti-angiogenesis agents on immune checkpoints expression are not fully understood. Method GBM-educated macrophages were generated from circulating monocytes of healthy controls and GBM patients under the education of GBM cell line. Surface expression of PD-L1 and VEGFR1 on GBM-educated macrophages was analyzed. VEGFR1 NAb and soluble VEGFR1 (sVEGFR1) were added and their effects on PD-L1 expression on TAMs was investigated. Serum soluble PD-L1 (sPD-L1) and sVEGFR1 levels in GBM patients were measured and their correlation was analyzed. Result The expression intensity of PD-L1 on GBM-educated macrophages was higher and its up-regulation partially depends on VEGFR1 signaling pathway. GBM-educated macrophages secreted less levels of soluble VEGFR1 (sVEGFR1), and exogenous sVEGFR1 down-regulated PD-L1 expression intensity. PD-L1 blockade promoted the secretion of sVEGFR1. Finally, sVEGFR1 and sPD-L1 in serum of GBM patients were overexpressed, and a positive correlation was found. Conclusion These findings reveal the interaction between PD-L1 and VEGFR1 signaling pathway in GBM-educated macrophages. VEGFR1 is involved with PD-L1 overexpression, which can be impeded by autocrine regulation of sVEGFR1. sVEGFR1 secretion by GBM-educated macrophages can be promoted by PD-L1 blockade. Taken together, these findings provide evidences for the combined application of ICIs and anti-angiogenesis therapies in the treatment of GBM.https://doi.org/10.1186/s12885-023-10733-5GlioblastomaTumor-associated macrophagesPD-L1sVEGFR1 |
| spellingShingle | Xin Liu Zhenke Li Jinxing Sun Zhijie Zhang Weiguo Li Interaction between PD-L1 and soluble VEGFR1 in glioblastoma-educated macrophages BMC Cancer Glioblastoma Tumor-associated macrophages PD-L1 sVEGFR1 |
| title | Interaction between PD-L1 and soluble VEGFR1 in glioblastoma-educated macrophages |
| title_full | Interaction between PD-L1 and soluble VEGFR1 in glioblastoma-educated macrophages |
| title_fullStr | Interaction between PD-L1 and soluble VEGFR1 in glioblastoma-educated macrophages |
| title_full_unstemmed | Interaction between PD-L1 and soluble VEGFR1 in glioblastoma-educated macrophages |
| title_short | Interaction between PD-L1 and soluble VEGFR1 in glioblastoma-educated macrophages |
| title_sort | interaction between pd l1 and soluble vegfr1 in glioblastoma educated macrophages |
| topic | Glioblastoma Tumor-associated macrophages PD-L1 sVEGFR1 |
| url | https://doi.org/10.1186/s12885-023-10733-5 |
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