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IGFBP2 promotes immunosuppression associated with its mesenchymal induction and FcγRIIB phosphorylation in glioblastoma
Immunotherapy shows a promise for treating glioblastoma (GBM), the most malignant and immunosuppressive glioma. The mesenchymal phenotype of cancer cells was frequently reported to be associated with their induction of immunosuppression within the cancer microenvironment. Overexpressed insulin-like...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6764691/ https://www.ncbi.nlm.nih.gov/pubmed/31560714 http://dx.doi.org/10.1371/journal.pone.0222999 |
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author | Liu, Yunmian Song, Chunyan Shen, Faping Zhang, Jing Song, Sonya Wei |
author_facet | Liu, Yunmian Song, Chunyan Shen, Faping Zhang, Jing Song, Sonya Wei |
author_sort | Liu, Yunmian |
collection | PubMed |
description | Immunotherapy shows a promise for treating glioblastoma (GBM), the most malignant and immunosuppressive glioma. The mesenchymal phenotype of cancer cells was frequently reported to be associated with their induction of immunosuppression within the cancer microenvironment. Overexpressed insulin-like growth factor binding protein 2 (IGFBP2) promotes GBM cell migration and invasion, and contributes to glioma progression and cancer recurrence and poor survival in GBM. However, whether IGFBP2 can induce immunosuppression in GBM was not reported yet. Thus, the study applied a syngeneic mouse GBM model, human GBM samples, and cancer-immune cell co-culture experiments to investigate the effect of IGFBP2 on GBM exposed immune cells and its association with the mesenchymal induction. We found that IGFBP2 promoted the mesenchymal feature of GBM cells. The inhibition of IGFBP2 relieved immunosuppression by increasing CD8(+) T and CD19(+) B cells and decreasing CD163(+) M2 macrophages. Further, the IGFBP2-promoted immunosuppression was associated with its induction of the mesenchymal feature of GBM cells and the inhibitory phosphorylated FcγRIIB of GBM exposed immune cells. Blocking IGFBP2 suppressed tumor growth and improved survival of tumor bearing mice in the mouse GBM model. These findings support the notion that targeting the IGFBP2 may present an effective immunotherapeutic strategy for mesenchymal GBMs. |
format | Online Article Text |
id | pubmed-6764691 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-67646912019-10-12 IGFBP2 promotes immunosuppression associated with its mesenchymal induction and FcγRIIB phosphorylation in glioblastoma Liu, Yunmian Song, Chunyan Shen, Faping Zhang, Jing Song, Sonya Wei PLoS One Research Article Immunotherapy shows a promise for treating glioblastoma (GBM), the most malignant and immunosuppressive glioma. The mesenchymal phenotype of cancer cells was frequently reported to be associated with their induction of immunosuppression within the cancer microenvironment. Overexpressed insulin-like growth factor binding protein 2 (IGFBP2) promotes GBM cell migration and invasion, and contributes to glioma progression and cancer recurrence and poor survival in GBM. However, whether IGFBP2 can induce immunosuppression in GBM was not reported yet. Thus, the study applied a syngeneic mouse GBM model, human GBM samples, and cancer-immune cell co-culture experiments to investigate the effect of IGFBP2 on GBM exposed immune cells and its association with the mesenchymal induction. We found that IGFBP2 promoted the mesenchymal feature of GBM cells. The inhibition of IGFBP2 relieved immunosuppression by increasing CD8(+) T and CD19(+) B cells and decreasing CD163(+) M2 macrophages. Further, the IGFBP2-promoted immunosuppression was associated with its induction of the mesenchymal feature of GBM cells and the inhibitory phosphorylated FcγRIIB of GBM exposed immune cells. Blocking IGFBP2 suppressed tumor growth and improved survival of tumor bearing mice in the mouse GBM model. These findings support the notion that targeting the IGFBP2 may present an effective immunotherapeutic strategy for mesenchymal GBMs. Public Library of Science 2019-09-27 /pmc/articles/PMC6764691/ /pubmed/31560714 http://dx.doi.org/10.1371/journal.pone.0222999 Text en © 2019 Liu et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Liu, Yunmian Song, Chunyan Shen, Faping Zhang, Jing Song, Sonya Wei IGFBP2 promotes immunosuppression associated with its mesenchymal induction and FcγRIIB phosphorylation in glioblastoma |
title | IGFBP2 promotes immunosuppression associated with its mesenchymal induction and FcγRIIB phosphorylation in glioblastoma |
title_full | IGFBP2 promotes immunosuppression associated with its mesenchymal induction and FcγRIIB phosphorylation in glioblastoma |
title_fullStr | IGFBP2 promotes immunosuppression associated with its mesenchymal induction and FcγRIIB phosphorylation in glioblastoma |
title_full_unstemmed | IGFBP2 promotes immunosuppression associated with its mesenchymal induction and FcγRIIB phosphorylation in glioblastoma |
title_short | IGFBP2 promotes immunosuppression associated with its mesenchymal induction and FcγRIIB phosphorylation in glioblastoma |
title_sort | igfbp2 promotes immunosuppression associated with its mesenchymal induction and fcγriib phosphorylation in glioblastoma |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6764691/ https://www.ncbi.nlm.nih.gov/pubmed/31560714 http://dx.doi.org/10.1371/journal.pone.0222999 |
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