Tumor progression is independent of tumor-associated macrophages in cell lineage-based mouse models of glioblastoma. Proc Natl Acad Sci U S A 2023 Apr 18;120(16):e2222084120
Date
04/12/2023Pubmed ID
37040416Pubmed Central ID
PMC10120014DOI
10.1073/pnas.2222084120Scopus ID
2-s2.0-85152244270 (requires institutional sign-in at Scopus site) 8 CitationsAbstract
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.
Author List
Chipman ME, Wang Z, Sun D, Pedraza AM, Bale TA, Parada LFAuthor
Daochun Sun PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBrain Neoplasms
Cell Lineage
Glioblastoma
Macrophages
Mice
Neoplastic Processes
Tumor Microenvironment
