Glioblastoma-instructed microglia transition to heterogeneous phenotypic states with phagocytic and dendritic cell-like features in patient tumors and patient-derived orthotopic xenografts DOI Creative Commons
Yahaya A Yabo, Pilar M. Moreno‐Sanchez, Yolanda Pires‐Afonso

и другие.

Genome Medicine, Год журнала: 2024, Номер 16(1)

Опубликована: Апрель 2, 2024

Abstract Background A major contributing factor to glioblastoma (GBM) development and progression is its ability evade the immune system by creating an immune-suppressive environment, where GBM-associated myeloid cells, including resident microglia peripheral monocyte-derived macrophages, play critical pro-tumoral roles. However, it unclear whether recruited cells are phenotypically functionally identical in GBM patients this heterogeneity recapitulated patient-derived orthotopic xenografts (PDOXs). thorough understanding of ecosystem recapitulation preclinical models currently missing, leading inaccurate results failures clinical trials. Methods Here, we report systematic characterization tumor microenvironment (TME) PDOXs patient tumors at single-cell spatial levels. We applied RNA sequencing, transcriptomics, multicolor flow cytometry, immunohistochemistry, functional studies examine heterogeneous TME instructed cells. representing different phenotypes were compared glioma mouse GL261 syngeneic model tumors. Results show that reciprocally interact with host create a patient-specific PDOXs. detected most prominent transcriptomic adaptations brain-resident main population cellular tumor, while peripheral-derived infiltrated brain sites blood–brain barrier disruption. More specifically, GBM-educated undergo transition diverse phenotypic states across distinct landscapes niches. subsets display phagocytic dendritic cell-like gene expression programs. Additionally, found novel microglial expressing cell cycle programs, astrocytic or endothelial markers. Lastly, temozolomide treatment leads plasticity altered crosstalk between adjacent components. Conclusions Our data provide insights into adaptation key role supporting growth response treatment. place as relevant assess functionality changes upon Graphical

Язык: Английский

Glioblastoma-instructed microglia transition to heterogeneous phenotypic states with phagocytic and dendritic cell-like features in patient tumors and patient-derived orthotopic xenografts DOI Creative Commons
Yahaya A Yabo, Pilar M. Moreno‐Sanchez, Yolanda Pires‐Afonso

и другие.

Genome Medicine, Год журнала: 2024, Номер 16(1)

Опубликована: Апрель 2, 2024

Abstract Background A major contributing factor to glioblastoma (GBM) development and progression is its ability evade the immune system by creating an immune-suppressive environment, where GBM-associated myeloid cells, including resident microglia peripheral monocyte-derived macrophages, play critical pro-tumoral roles. However, it unclear whether recruited cells are phenotypically functionally identical in GBM patients this heterogeneity recapitulated patient-derived orthotopic xenografts (PDOXs). thorough understanding of ecosystem recapitulation preclinical models currently missing, leading inaccurate results failures clinical trials. Methods Here, we report systematic characterization tumor microenvironment (TME) PDOXs patient tumors at single-cell spatial levels. We applied RNA sequencing, transcriptomics, multicolor flow cytometry, immunohistochemistry, functional studies examine heterogeneous TME instructed cells. representing different phenotypes were compared glioma mouse GL261 syngeneic model tumors. Results show that reciprocally interact with host create a patient-specific PDOXs. detected most prominent transcriptomic adaptations brain-resident main population cellular tumor, while peripheral-derived infiltrated brain sites blood–brain barrier disruption. More specifically, GBM-educated undergo transition diverse phenotypic states across distinct landscapes niches. subsets display phagocytic dendritic cell-like gene expression programs. Additionally, found novel microglial expressing cell cycle programs, astrocytic or endothelial markers. Lastly, temozolomide treatment leads plasticity altered crosstalk between adjacent components. Conclusions Our data provide insights into adaptation key role supporting growth response treatment. place as relevant assess functionality changes upon Graphical

Язык: Английский

Процитировано

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