Dataset Information

LRIG2 promotes glioblastoma progression by modulating innate antitumor immunity through macrophage infiltration and polarization.

ABSTRACT:

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.

SUBMITTER: Hu J

PROVIDER: S-EPMC9472135 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

LRIG2 promotes glioblastoma progression by modulating innate antitumor immunity through macrophage infiltration and polarization.

Hu Jinyang J Dong Feng F He You Y Xia Xianyou X Cheng Fangling F Chen Sui S Hou Xiaoshuang X Zhang Po P Liu Guohao G Li Ying Y Gao Qian Q Dong Minhai M Li Ting T Li Wei W Xiao Qungen Q Li Xiaopeng X Yu Xingjiang X Xi Guifa G Guo Dongsheng D Wu Xudong X Wang Baofeng B

Journal for immunotherapy of cancer 20220901 9

<h4>Background</h4>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).<h4>Results</h4>High level of LRIG2/soluble LRIG2 (sLRIG2) expression activates immune-related signaling pathways, which are associated with poor pro ...[more]

PMID: 36096529

Similar Datasets

Project description:BackgroundAccumulating evidence suggests that M2-polarized tumor-associated macrophages (TAMs) play an important role in cancer progression and metastasis, making M2 polarization of TAMs an ever more appealing target for therapeutic intervention. Astragaloside IV (AS-IV), a saponin component isolated from Astragali radix, has been reported to inhibit the invasion and metastasis of lung cancer, but its effects on TAMs during lung cancer progression have not been investigated.MethodsHuman THP-1 monocytes were induced to differentiate into M2 macrophages through treatments with IL-4, IL-13, and phorbol myristate acetate (PMA). We used the lung cancer cell lines A549 and H1299 cultured in conditioned medium from M2 macrophages (M2-CM) to investigate the effects of AS-IV on tumor growth, invasion, migration, and angiogenesis of lung cancer cells. Macrophage subset distribution, M1 and M2 macrophage-associated markers, and mRNA expression were analyzed by flow cytometry and quantitative PCR. The activation of adenosine monophosphate-activated protein kinase (AMPK) signaling pathways that mediate M2-CM-promoted tumor migration was detected using western blotting.ResultsHere we found that AS-IV significantly inhibited IL-13 and IL-4-induced M2 polarization of macrophages, as illustrated by reduced expression of CD206 and M2-associated genes, and that AS-IV suppressed the M2-CM-induced invasion, migration, and angiogenesis of A549 and H1299 cells. In vivo experiments demonstrated that AS-IV greatly inhibited tumor growth and reduced the number of metastases of Lewis lung cancer. The percentage of M2 macrophages was decreased in tumor tissue after AS-IV treatment. Furthermore, AS-IV inhibited AMPKα activation in M2 macrophages, and silencing of AMPKα partially abrogated the inhibitory effect of AS-IV.ConclusionsAS-IV reduced the growth, invasion, migration, and angiogenesis of lung cancer by blocking the M2 polarization of macrophages partially through the AMPK signaling pathway, which appears to play an important role in AS-IV's ability to inhibit the metastasis of lung cancer.

Dataset Information

LRIG2 promotes glioblastoma progression by modulating innate antitumor immunity through macrophage infiltration and polarization.

Background

Results

Conclusions

Publications

LRIG2 promotes glioblastoma progression by modulating innate antitumor immunity through macrophage infiltration and polarization.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets