Isolation of Human Circulating Myeloid-Derived Suppressor Cells and Analysis of Their Immunosuppressive Activity

Bruderek, Kirsten; Schirrmann, R; Brandau, Sven

doi:10.1007/978-1-0716-1060-2_5

Cited by 2 publications

(1 citation statement)

References 6 publications

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“…Based on this work, they established a standard protocol for isolation, identification, and characterization of human MDSC 91 . Moreover, our group has provided a flow cytometry analysis strategy for immunophenotyping of MDSC 92 as well as assays to evaluate immunosuppressive functions of these cells over T cells, including dye dilution proliferation assay and detection of IFN‐γ production by T cells using sandwich ELISA 93 …”

Section: Mdsc Concept: Strength and Weaknessmentioning

confidence: 99%

N1 versus N2 and PMN‐MDSC: A critical appraisal of current concepts on tumor‐associated neutrophils and new directions for human oncology

Antuamwine

Bosnjakovic

Hofmann‐Vega

et al. 2022

Immunological Reviews

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Summary Research on tumor‐associated neutrophils (TAN) currently surges because of the well‐documented strong clinical relevance of tumor‐infiltrating neutrophils. This relevance is illustrated by strong correlations between high frequencies of intratumoral neutrophils and poor outcome in the majority of human cancers. Recent high‐dimensional analysis of murine neutrophils provides evidence for unexpected plasticity of neutrophils in murine models of cancer and other inflammatory non‐malignant diseases. New analysis tools enable deeper insight into the process of neutrophil differentiation and maturation. These technological and scientific developments led to the description of an ever‐increasing number of distinct transcriptional states and associated phenotypes in murine models of disease and more recently also in humans. At present, functional validation of these different transcriptional states and potential phenotypes in cancer is lacking. Current functional concepts on neutrophils in cancer rely mainly on the myeloid‐derived suppressor cell (MDSC) concept and the dichotomous and simple N1–N2 paradigm. In this manuscript, we review the historic development of those concepts, critically evaluate these concepts against the background of our own work and provide suggestions for a refinement of current concepts in order to facilitate the transition of TAN research from experimental insight to clinical translation.

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Section: Mdsc Concept: Strength and Weaknessmentioning

confidence: 99%

N1 versus N2 and PMN‐MDSC: A critical appraisal of current concepts on tumor‐associated neutrophils and new directions for human oncology

Antuamwine

Bosnjakovic

Hofmann‐Vega

et al. 2022

Immunological Reviews

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Tumor-derived GLI1 promotes remodeling of the immune tumor microenvironment in melanoma

Giammona,

De Vellis,

Crivaro

et al. 2024

J Exp Clin Cancer Res

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Background Melanoma progression is based on a close interaction between cancer cells and immune cells in the tumor microenvironment (TME). Thus, a better understanding of the mechanisms controlling TME dynamics and composition will help improve the management of this dismal disease. Work from our and other groups has reported the requirement of an active Hedgehog-GLI (HH-GLI) signaling for melanoma growth and stemness. However, the role of the downstream GLI1 transcription factor in melanoma TME remains largely unexplored. Methods The immune-modulatory activity of GLI1 was evaluated in a syngeneic B16F10 melanoma mouse model assessing immune populations by flow cytometry. Murine polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) were differentiated from bone marrow cells and their immunosuppressive ability was assessed by inhibition of T cells. Conditioned media (CM) from GLI1-overexpressing mouse melanoma cells was used to culture PMN-MDSCs, and the effects of CM were evaluated by Transwell invasion assay and T cell inhibition. Cytokine array analysis, qPCR and chromatin immunoprecipitation were performed to explore the regulation of CX3CL1 expression by GLI1. Human monocyte-derived dendritic cells (moDCs) were cultured in CM from GLI1-silenced patient-derived melanoma cells to assess their activation and recruitment. Blocking antibodies anti-CX3CL1, anti-CCL7 and anti-CXCL8 were used for in vitro functional assays. Results Melanoma cell-intrinsic activation of GLI1 promotes changes in the infiltration of immune cells, leading to accumulation of immunosuppressive PMN-MDSCs and regulatory T cells, and to decreased infiltration of dendric cells (DCs), CD8 + and CD4 + T cells in the TME. In addition, we show that ectopic expression of GLI1 in melanoma cells enables PMN-MDSC expansion and recruitment, and increases their ability to inhibit T cells. The chemokine CX3CL1, a direct transcriptional target of GLI1, contributes to PMN-MDSC expansion and recruitment. Finally, silencing of GLI1 in patient-derived melanoma cells promotes the activation of human monocyte-derived dendritic cells (moDCs), increasing cytoskeleton remodeling and invasion ability. This phenotype is partially prevented by blocking the chemokine CCL7, but not CXCL8. Conclusion Our findings highlight the relevance of tumor-derived GLI1 in promoting an immune-suppressive TME, which allows melanoma cells to evade the immune system, and pave the way for the design of new combination treatments targeting GLI1.

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Isolation of Human Circulating Myeloid-Derived Suppressor Cells and Analysis of Their Immunosuppressive Activity

Cited by 2 publications

References 6 publications

N1 versus N2 and PMN‐MDSC: A critical appraisal of current concepts on tumor‐associated neutrophils and new directions for human oncology

N1 versus N2 and PMN‐MDSC: A critical appraisal of current concepts on tumor‐associated neutrophils and new directions for human oncology

Tumor-derived GLI1 promotes remodeling of the immune tumor microenvironment in melanoma

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