학술논문
Single-cell RNA sequencing reveals immunosuppressive myeloid cell diversity during malignant progression in a murine model of glioma
Document Type
article
Author
Sakthi Rajendran; Yang Hu; Alessandro Canella; Clayton Peterson; Amy Gross; Maren Cam; Matthew Nazzaro; Abigail Haffey; Akdes Serin-Harmanci; Rosario Distefano; Giovanni Nigita; Wesley Wang; Daniel Kreatsoulas; Zihai Li; Jesse A. Sepeda; Andrew Sas; Mark E. Hester; Katherine E. Miller; Olivier Elemento; Ryan D. Roberts; Eric C. Holland; Ganesh Rao; Elaine R. Mardis; Prajwal Rajappa
Source
Cell Reports, Vol 42, Iss 3, Pp 112197- (2023)
Subject
Language
English
ISSN
2211-1247
Abstract
Summary: Recent studies have shown the importance of the dynamic tumor microenvironment (TME) in high-grade gliomas (HGGs). In particular, myeloid cells are known to mediate immunosuppression in glioma; however, it is still unclear if myeloid cells play a role in low-grade glioma (LGG) malignant progression. Here, we investigate the cellular heterogeneity of the TME using single-cell RNA sequencing in a murine glioma model that recapitulates the malignant progression of LGG to HGG. LGGs show increased infiltrating CD4+ and CD8+ T cells and natural killer (NK) cells in the TME, whereas HGGs abrogate this infiltration. Our study identifies distinct macrophage clusters in the TME that show an immune-activated phenotype in LGG but then evolve to an immunosuppressive state in HGG. We identify CD74 and macrophage migration inhibition factor (MIF) as potential targets for these distinct macrophage populations. Targeting these intra-tumoral macrophages in the LGG stage may attenuate their immunosuppressive properties and impair malignant progression.