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Tumor-associated hematopoietic stem and progenitor cells positively linked to glioblastoma progression

ABSTRACT: Brain tumors are typically immunosuppressive and refractory to immunotherapies for reasons that remain poorly understood. The unbiased profiling of immune cell types in the tumor microenvironment may reveal immunologic networks affecting therapy and course of disease. Here we identify and validate the presence of hematopoietic stem and progenitor cells (HSPCs) within tumor tissues that are positively linked to glioblastoma malignancy. In contrast to the medullary hematopoietic compartment, tumor-associated HSPCs are comprised of a majority of CD38- immature cells, such as hematopoietic stem cells and multipotent progenitors, express genes related to glioblastoma progression and display patterns of accelerated cell cycle. When cultured ex vivo, tumor-associated HSPCs form prevalently myeloid colonies, suggesting potential in situ myelopoiesis. In experimental models, HSPCs promote tumor cell proliferation, expression of the immune checkpoint PD-L1 and secretion of tumor promoting cytokines such as IL-6, IL-8 and CCL2, indicating concomitant support of both malignancy and immunosuppression. Additionally, the frequency of tumor-associated HSPCs is prognostic for patient survival and correlate with immunosuppressive phenotypes. These findings identify a new element in the complex landscape of glioblastoma that may serve as an independent prognostic factor or target for brain tumor immunotherapies.

ORGANISM(S): Homo sapiens

PROVIDER: GSE165238 | GEO | 2021/05/25

REPOSITORIES: GEO

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