IGFBP2 promotes immunosuppression associated with its mesenchymal induction and FcγRIIB phosphorylation in glioblastoma
| Autor: | Jing Zhang, Sonya Wei Song, Yunmian Liu, Chunyan Song, Faping Shen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
B Cells medicine.medical_treatment Cancer Treatment Datasets as Topic Kaplan-Meier Estimate urologic and male genital diseases Pathology and Laboratory Medicine Biochemistry White Blood Cells Mice 0302 clinical medicine Animal Cells Cell Movement Medicine and Health Sciences Tumor Microenvironment Post-Translational Modification Phosphorylation Neurological Tumors Multidisciplinary biology Brain Neoplasms Immunosuppression Cell migration Glioma female genital diseases and pregnancy complications Gene Expression Regulation Neoplastic Oncology Neurology 030220 oncology & carcinogenesis Gene Knockdown Techniques Medicine Female Cellular Types Research Article Science Immune Cells Immunology Research and Analysis Methods Immune Suppression CD19 03 medical and health sciences Immune system Signs and Symptoms Diagnostic Medicine Cell Line Tumor medicine Animals Humans Antibody-Producing Cells Immunohistochemistry Techniques Cell Proliferation Blood Cells business.industry urogenital system Macrophages Gene Expression Profiling Mesenchymal stem cell Receptors IgG Biology and Life Sciences Cancers and Neoplasms Proteins Immunotherapy Cell Biology medicine.disease Coculture Techniques nervous system diseases Histochemistry and Cytochemistry Techniques Disease Models Animal Insulin-Like Growth Factor Binding Protein 2 030104 developmental biology Tissue Array Analysis Cancer cell Cancer research biology.protein Immunologic Techniques Tumor Escape business Glioblastoma |
| Zdroj: | PLoS ONE PLoS ONE, Vol 14, Iss 9, p e0222999 (2019) |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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