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Origin and Function of Tumor-Associated Macrophages and Mesenchymal Stromal Cells in GBM Subtypes

Objective

One of the key goals to understand GBM biology and find strategies to treat this deadly tumor is to define the different cell populations within the tumor. The inter-tumor heterogeneity among GBM patients, investigated on a molecular level, has led to the identification of three main subtypes; the proneural (PN), mesenchymal (MES), and classical (CL), which are associated with specific mutations. The different properties of the three subgroups play an important role in the clinical response and the pathology of the tumor. The tumor microenvironment, that play an important role in tumor heterogeneity, is built up by multiple factors including recruited cells, blood vessels, secreted cytokines, and extracellular matrix. However, the constitution of these factors in each subtype is not known. In this work, we will characterize the cells that are recruited to the different GBM subtypes focusing on tumor-associated macrophages (TAMs) and mesenchymal stromal cells (MSCs). For this purpose, transgenic mice representing the three glioma subtypes will be used. Chimeric mice will be utilized to investigate the origin of the recruited cells. Flow cytometry, confocal analysis, multiplex assays and single-cell gene expression analysis will be used to characterize the tumor cells and the recruited cells to find master regulatory elements of recruitment. Therapeutic targeting will follow identification of master regulatory factors that recruit TAMs and MSCs to the tumor.

Call for proposal

H2020-MSCA-IF-2018
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Funding Scheme

MSCA-IF-GF - Global Fellowships

Coordinator

KAROLINSKA INSTITUTET
Address
Nobels Vag 5
17177 Stockholm
Sweden
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 261 192

Participants (1)

GOETEBORGS UNIVERSITET

Participation ended

Sweden
EU contribution
€ 0
Address
Vasaparken
405 30 Goeteborg
Activity type
Higher or Secondary Education Establishments

Partners (2)

EMORY UNIVERSITY NON PROFIT CORP

Participation ended

United States
Address
Clifton Road, Ne, 4Th Floor 1599
30322 Atlanta
Activity type
Higher or Secondary Education Establishments
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
United States
Address
One Gustave L Levy Place Box 1075
10029 6574 New York
Activity type
Higher or Secondary Education Establishments