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LRIG2 promotes glioblastoma progression by modulating innate antitumor immunity through macrophage infiltration and polarization
BACKGROUND: Glioblastoma (GBM) is the most common malignant brain tumor with poor clinical outcomes. Immunotherapy has recently been an attractive and promising treatment of extracranial malignancies, however, most of clinical trials for GBM immunotherapy failed due to predominant accumulation of tu...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BMJ Publishing Group
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9472135/ https://www.ncbi.nlm.nih.gov/pubmed/36096529 http://dx.doi.org/10.1136/jitc-2021-004452 |
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author | Hu, Jinyang Dong, Feng He, You Xia, Xianyou Cheng, Fangling Chen, Sui Hou, Xiaoshuang Zhang, Po Liu, Guohao Li, Ying Gao, Qian Dong, Minhai Li, Ting Li, Wei Xiao, Qungen Li, Xiaopeng Yu, Xingjiang Xi, Guifa Guo, Dongsheng Wu, Xudong Wang, Baofeng |
author_facet | Hu, Jinyang Dong, Feng He, You Xia, Xianyou Cheng, Fangling Chen, Sui Hou, Xiaoshuang Zhang, Po Liu, Guohao Li, Ying Gao, Qian Dong, Minhai Li, Ting Li, Wei Xiao, Qungen Li, Xiaopeng Yu, Xingjiang Xi, Guifa Guo, Dongsheng Wu, Xudong Wang, Baofeng |
author_sort | Hu, Jinyang |
collection | PubMed |
description | BACKGROUND: Glioblastoma (GBM) is the most common malignant brain tumor with poor clinical outcomes. Immunotherapy has recently been an attractive and promising treatment of extracranial malignancies, however, most of clinical trials for GBM immunotherapy failed due to predominant accumulation of tumor-associated microglia/macrophages (TAMs). RESULTS: High level of LRIG2/soluble LRIG2 (sLRIG2) expression activates immune-related signaling pathways, which are associated with poor prognosis in GBM patients. LRIG2/sLRIGs promotes CD47 expression and facilitates TAM recruitment. Blockade of CD47–SIRPα interactions and inhibition of sLRIG2 secretion synergistically suppress GBM progression in an orthotropic murine GBM model. CONCLUSIONS: GBM cells with high level LRIG2 escape the phagocytosis by TAM via the CD47-SIRPα axis, highlighting a necessity for an early stage of clinical trial targeting LRIG2 and CD47-SIRPα as a novel treatment for patients with GBM. |
format | Online Article Text |
id | pubmed-9472135 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-94721352022-09-15 LRIG2 promotes glioblastoma progression by modulating innate antitumor immunity through macrophage infiltration and polarization Hu, Jinyang Dong, Feng He, You Xia, Xianyou Cheng, Fangling Chen, Sui Hou, Xiaoshuang Zhang, Po Liu, Guohao Li, Ying Gao, Qian Dong, Minhai Li, Ting Li, Wei Xiao, Qungen Li, Xiaopeng Yu, Xingjiang Xi, Guifa Guo, Dongsheng Wu, Xudong Wang, Baofeng J Immunother Cancer Basic Tumor Immunology BACKGROUND: Glioblastoma (GBM) is the most common malignant brain tumor with poor clinical outcomes. Immunotherapy has recently been an attractive and promising treatment of extracranial malignancies, however, most of clinical trials for GBM immunotherapy failed due to predominant accumulation of tumor-associated microglia/macrophages (TAMs). RESULTS: High level of LRIG2/soluble LRIG2 (sLRIG2) expression activates immune-related signaling pathways, which are associated with poor prognosis in GBM patients. LRIG2/sLRIGs promotes CD47 expression and facilitates TAM recruitment. Blockade of CD47–SIRPα interactions and inhibition of sLRIG2 secretion synergistically suppress GBM progression in an orthotropic murine GBM model. CONCLUSIONS: GBM cells with high level LRIG2 escape the phagocytosis by TAM via the CD47-SIRPα axis, highlighting a necessity for an early stage of clinical trial targeting LRIG2 and CD47-SIRPα as a novel treatment for patients with GBM. BMJ Publishing Group 2022-09-12 /pmc/articles/PMC9472135/ /pubmed/36096529 http://dx.doi.org/10.1136/jitc-2021-004452 Text en © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) . |
spellingShingle | Basic Tumor Immunology Hu, Jinyang Dong, Feng He, You Xia, Xianyou Cheng, Fangling Chen, Sui Hou, Xiaoshuang Zhang, Po Liu, Guohao Li, Ying Gao, Qian Dong, Minhai Li, Ting Li, Wei Xiao, Qungen Li, Xiaopeng Yu, Xingjiang Xi, Guifa Guo, Dongsheng Wu, Xudong Wang, Baofeng LRIG2 promotes glioblastoma progression by modulating innate antitumor immunity through macrophage infiltration and polarization |
title | LRIG2 promotes glioblastoma progression by modulating innate antitumor immunity through macrophage infiltration and polarization |
title_full | LRIG2 promotes glioblastoma progression by modulating innate antitumor immunity through macrophage infiltration and polarization |
title_fullStr | LRIG2 promotes glioblastoma progression by modulating innate antitumor immunity through macrophage infiltration and polarization |
title_full_unstemmed | LRIG2 promotes glioblastoma progression by modulating innate antitumor immunity through macrophage infiltration and polarization |
title_short | LRIG2 promotes glioblastoma progression by modulating innate antitumor immunity through macrophage infiltration and polarization |
title_sort | lrig2 promotes glioblastoma progression by modulating innate antitumor immunity through macrophage infiltration and polarization |
topic | Basic Tumor Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9472135/ https://www.ncbi.nlm.nih.gov/pubmed/36096529 http://dx.doi.org/10.1136/jitc-2021-004452 |
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