Proliferative tumor associated macrophages exhibit tumor memory and pro mutational gene signature in glioblastoma

ABSTRACT: Glioblastoma exhibits a complex, diverse and dynamic immune microenvironment, yet its spatial immune complexity in hypoxic and normoxic regions remains unknown. Understanding cellular interactions and distributions is vital for developing efficient therapeutic strategies. Here, we present spatially resolved single-cell imaging mass cytometry (IMC), multiplexed imaging, single-cell mRNA sequencing and functional analyses of tumor-associated macrophages/microglia in glioblastoma patients. We identify a population of tumor-associated macrophages in the pseudo-palisading niche that possess high proliferative capability, termed Pro-TAMs. Tumor-associated memory macrophage (MTAM) exhibit (characterized by the CD45RO surface marker) and express mutagenesis-promoting genes APOBEC3B and APOBEC3C, which influence intratumoral mutational burden and evolution. High expression of Pro-TAM gene signatures strongly correlates with tumor mutational burden and poor patient survival in glioblastoma. This study sheds light on a potential novel role of TAMs in tumor mutagenesis and tumor evolution, emphasizing their spatial cellular complexity and the diagnostic implications thereof. We also reveal the obstacles and possibilities that need to be considered in developing new therapeutic strategies for glioblastoma.

ORGANISM(S): Homo sapiens

PROVIDER: GSE277584 | GEO | 2026/06/30

REPOSITORIES: GEO