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

I-Na Lu, Celia Dobersalske, Laurèl Rauschenbach, Sarah Teuber-Hanselmann, Anita Steinbach, Vivien Ullrich, Shruthi Prasad, Tobias Blau, Sied Kebir, Jens T. Siveke, Jürgen C. Becker, Ulrich Sure, Martin Glas, Björn Scheffler and Igor Cima ()
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I-Na Lu: DKFZ-Division Translational Neurooncology at the West German Cancer Center (WTZ), University Hospital Essen/University of Duisburg-Essen
Celia Dobersalske: DKFZ-Division Translational Neurooncology at the West German Cancer Center (WTZ), University Hospital Essen/University of Duisburg-Essen
Laurèl Rauschenbach: DKFZ-Division Translational Neurooncology at the West German Cancer Center (WTZ), University Hospital Essen/University of Duisburg-Essen
Sarah Teuber-Hanselmann: Institute of Neuropathology, University Hospital Essen
Anita Steinbach: DKFZ-Division Translational Neurooncology at the West German Cancer Center (WTZ), University Hospital Essen/University of Duisburg-Essen
Vivien Ullrich: DKFZ-Division Translational Neurooncology at the West German Cancer Center (WTZ), University Hospital Essen/University of Duisburg-Essen
Shruthi Prasad: DKFZ-Division Translational Neurooncology at the West German Cancer Center (WTZ), University Hospital Essen/University of Duisburg-Essen
Tobias Blau: Institute of Neuropathology, University Hospital Essen
Sied Kebir: DKFZ-Division Translational Neurooncology at the West German Cancer Center (WTZ), University Hospital Essen/University of Duisburg-Essen
Jens T. Siveke: German Cancer Research Center (DKFZ)
Jürgen C. Becker: German Cancer Research Center (DKFZ)
Ulrich Sure: German Cancer Consortium (DKTK)
Martin Glas: DKFZ-Division Translational Neurooncology at the West German Cancer Center (WTZ), University Hospital Essen/University of Duisburg-Essen
Björn Scheffler: DKFZ-Division Translational Neurooncology at the West German Cancer Center (WTZ), University Hospital Essen/University of Duisburg-Essen
Igor Cima: DKFZ-Division Translational Neurooncology at the West German Cancer Center (WTZ), University Hospital Essen/University of Duisburg-Essen

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: 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 glioblastoma tissues. Furthermore, we demonstrate a positive link of tumor-associated HSPCs with malignant and immunosuppressive phenotypes. Compared to the medullary hematopoietic compartment, tumor-associated HSPCs contain a higher fraction of immunophenotypically and transcriptomically immature, CD38- cells, such as hematopoietic stem cells and multipotent progenitors, express genes related to glioblastoma progression and display signatures of active cell cycle phases. When cultured ex vivo, tumor-associated HSPCs form 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. In patients, the amount of tumor-associated HSPCs in tumor tissues is prognostic for patient survival and correlates with immunosuppressive phenotypes. These findings identify an important element in the complex landscape of glioblastoma that may serve as a target for brain tumor immunotherapies.

Date: 2021
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DOI: 10.1038/s41467-021-23995-z

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