Tumor progression is independent of tumor-associated macrophages in cell lineage-based mouse models of glioblastoma Journal Article

   

Authors:	Chipman, M. E.; Wang, Z.; Sun, D.; Pedraza, A. M.; Bale, T. A.; Parada, L. F.
Article Title:	Tumor progression is independent of tumor-associated macrophages in cell lineage-based mouse models of glioblastoma
Abstract:	Macrophage targeting therapies have had limited clinical success in glioblastoma (GBM). Further understanding the GBM immune microenvironment is critical for refining immunotherapeutic approaches. Here, we use genetically engineered mouse models and orthotopic transplantation-based GBM models with identical driver mutations and unique cells of origin to examine the role of tumor cell lineage in shaping the immune microenvironment and response to tumor-associated macrophage (TAM) depletion therapy. We show that oligodendrocyte progenitor cell lineage-associated GBMs (Type 2) recruit more immune infiltrates and specifically monocyte-derived macrophages than subventricular zone neural stem cell-associated GBMs (Type 1). We then devise a TAM depletion system that offers a uniquely robust and sustained TAM depletion. We find that extensive TAM depletion in these cell lineage-based GBM models affords no survival benefit. Despite the lack of survival benefit of TAM depletion, we show that Type 1 and Type 2 GBMs have unique molecular responses to TAM depletion. In sum, we demonstrate that GBM cell lineage influences TAM ontogeny and abundance and molecular response to TAM depletion.
Keywords:	brain tumor; brain neoplasms; mouse; animal; metabolism; animals; mice; pathology; cell lineage; glioblastoma; macrophage; macrophages; cell of origin; oncogenesis and malignant transformation; neoplastic processes; tumor microenvironment; microglia; tumor-associated macrophages; csf1r inhibition
Journal Title:	Proceedings of the National Academy of Sciences of the United States of America
Volume:	120
Issue:	16
ISSN:	0027-8424
Publisher:	National Academy of Sciences
Date Published:	2023-04-18
Start Page:	e2222084120
Language:	English
DOI:	10.1073/pnas.2222084120
PUBMED:	37040416
PROVIDER:	scopus
PMCID:	PMC10120014
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85152244270&doi=10.1073%2fpnas.2222084120&partnerID=40&md5=98f44b9e12c2d5a8782bc1dc113bf117
Notes:	The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Corresponding author is MSK author: Luis F. Parada -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/205668