Dataset Information

Tumor-associated macrophage infiltration in meningioma.

ABSTRACT:

Background

Meningioma, a most common brain tumor, has a high rate of recurrence. Tumor-associated macrophages (TAMs) are the most abundant immune cell type in meningioma. TAMs display functional phenotypic diversity and may establish either an inflammatory and anti-tumoral or an immunosuppressive and pro-tumoral microenvironment. TAM subtypes present in meningioma and potential contribution to growth and recurrence is unknown.

Methods

Immunofluorescence staining was used to quantify M1 and M2 TAM populations in tissues obtained from 30 meningioma patients. Associations between M1 and M2 cells, M1:M2 cell ratio to tumor characteristics, WHO grade, recurrence, size, location, peri-tumoral edema, and patient demographics such as age and sex were examined.

Results

TAM cells accounted for ~18% of all cells in meningioma tissues. More than 80% of infiltrating TAMs were found to be of pro-tumoral M2 phenotype and correlated to tumor size (P = .0409). M1:M2 cell ratio was significantly decreased in WHO grade II, compared to grade I tumors (P = .009). Furthermore, a 2.3-fold difference in M1:M2 ratio between primary (0.14) and recurrent (0.06) tumors was observed (n = 18 and 12 respectively, P = .044).

Conclusion

This study is the first to confirm existence of pro-tumoral M2 TAMs in the meningioma microenvironment, emphasizing its potential role in tumor growth and recurrence.

SUBMITTER: Proctor DT

PROVIDER: S-EPMC7212927 | biostudies-literature | 2019 May-Dec

REPOSITORIES: biostudies-literature

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Publications

Tumor-associated macrophage infiltration in meningioma.

Proctor Dustin T DT Huang Jordan J Lama Sanju S Albakr Abdulrahman A Van Marle Guido G Sutherland Garnette R GR

Neuro-oncology advances 20190501 1

<h4>Background</h4>Meningioma, a most common brain tumor, has a high rate of recurrence. Tumor-associated macrophages (TAMs) are the most abundant immune cell type in meningioma. TAMs display functional phenotypic diversity and may establish either an inflammatory and anti-tumoral or an immunosuppressive and pro-tumoral microenvironment. TAM subtypes present in meningioma and potential contribution to growth and recurrence is unknown.<h4>Methods</h4>Immunofluorescence staining was used to quanti ...[more]

PMID: 32642654

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Project description:BACKGROUND: Tumor-associated macrophages (TAM) play an important role in tumor microenvironment. Particularly, M2 macrophages contribute to tumor progression, depending on the expression of NF-?B. Tumor-derived exosomes can modulate tumor microenvironment by transferring miRNAs to immune cells. Epigallocatechin gallate (EGCG) has well known anti-tumor effects; however, no data are available on the influence of EGCG on communication with cancer cells and TAM. METHODS: Murine breast cancer cell lines, 4T1, was used for in vivo and ex vivo studies. Exosome was extracted from EGCG-treated 4T1 cells, and the change of miRNAs was screened using microarray. Tumor cells or TAM isolated from murine tumor graft were incubated with exosomes derived from EGCG-treated and/or miR-16 inhibitor-transfected 4T1 cells. Chemokines for monocytes (CSF-1 and CCL-2), cytokines both with high (IL-6 and TGF-?) and low (TNF-?) expression in M2 macrophages, and molecules in NF-?B pathway (IKK? and I?-B) were evaluated by RT-qPCR or western blot. RESULTS: EGCG suppressed tumor growth in murine breast cancer model, which was associated with decreased TAM and M2 macrophage infiltration. Expression of chemokine for monocytes (CSF-1 and CCL-2) were low in tumor cells from EGCG-treated mice, and cytokines of TAM was skewed from M2- into M1-like phenotype by EGCG as evidenced by decreased IL-6 and TGF-? and increased TNF-?. Ex vivo incubation of isolated tumor cells with EGCG inhibited the CSF-1 and CCL-2 expression. Ex vivo incubation of TAM with exosomes from EGCG-treated 4T1 cells led to IKK? suppression and concomitant I-?B accumulation; increase of IL-6 and TGF-?; and, decrease of TNF-?. EGCG up-regulated miR-16 in 4T1 cells and in the exosomes. Treatment of tumor cells or TAM with exosomes derived from EGCG-treated and miR-16-knock-downed 4T1 cells restored the above effects on chemokines, cytokines, and NF-?B pathway elicited by EGCG-treated exosomes. CONCLUSIONS: Our data demonstrate that EGCG up-regulates miR-16 in tumor cells, which can be transferred to TAM via exosomes and inhibits TAM infiltration and M2 polarization. We suggest a novel mechanism by which EGCG exerts anti-tumor activity via regulation of TAM in tumor microenvironment.

Project description:BackgroundDiffuse gliomas are the most common malignant tumors of the central nervous system with poor treatment efficacy. Infiltration of immune cells into tumors during immunosurveillance is observed in multiple tumor entities and often associated with a favorable outcome. The aim of this study was to evaluate the infiltration of immune cells in gliomas and their association with cerebrospinal fluid (CSF) cytokine concentrations.MethodsWe applied immunohistochemistry in tumor tissue sections of 18 high-grade glioma (HGG) patients (4 anaplastic astrocytoma, IDH-wildtype WHO-III; 14 glioblastomas (GBM), IDH-wildtype WHO-IV) in order to assess and quantify leucocytes (CD45) and macrophages (CD68, CD163) within the tumor core, infiltration zone and perivascular spaces. In addition, we quantified the concentrations of 30 cytokines in the same patients' CSF and in 14 non-inflammatory controls.ResultsWe observed a significantly higher percentage of CD68+ macrophages (21-27%) in all examined tumor areas when compared to CD45+ leucocytes (ca. 3-7%); CD163+ cell infiltration was between 5 and 15%. Compared to the tumor core, significantly more macrophages and leucocytes were detectable within the perivascular area. The brain parenchyma showing a lower tumor cell density seems to be less infiltrated by macrophages. Interleukin (IL)-7 was significantly downregulated in CSF of GBM patients compared to controls. Additionally, CD68+ macrophage infiltrates showed significant correlations with the expression of eotaxin, interferon-γ, IL-1β, IL-2, IL-10, IL-13, IL-16 and vascular endothelial growth factor.ConclusionsOur findings suggest that the infiltration of lymphocytes is generally low in HGG, and does not correlate with cytokine concentrations in the CSF. In contrast, macrophage infiltrates in HGG are associated with CSF cytokine changes that possibly shape the tumor microenvironment. Although results point towards an escape from immunosurveillance or even exploitation of immune cells by HGG, further studies are necessary to decipher the exact role of the immune system in these tumors.

Dataset Information

Tumor-associated macrophage infiltration in meningioma.

Background

Methods

Results

Conclusion

Publications

Tumor-associated macrophage infiltration in meningioma.

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