Myeloid progenitor dysregulation fuels immunosuppressive macrophages in tumors.
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ABSTRACT:
PROVIDER: PRJNA1125337 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Myeloid progenitor dysregulation fuels immunosuppressive macrophages in tumors [dataset 1]
| PRJNA1074689 | ENA
Project description:Myeloid progenitor dysregulation fuels immunosuppressive macrophages in tumors [dataset 2]
| PRJNA1125112 | ENA
Project description:Myeloid progenitor dysregulation fuels immunosuppressive macrophages in tumors [dataset 3]
| PRJNA1224233 | ENA
Project description:Monocyte–derived macrophages (mo-macs) often drive immunosuppression in the tumor microenvironment (TME) and tumor-enhanced myelopoiesis in the bone marrow (BM) fuels these populations. Here, we performed paired transcriptome and chromatin accessibility analysis over the continuum of myeloid progenitors, circulating monocytes, and tumor-infiltrating mo-macs in mice and in patients with lung cancer to identify myeloid progenitor programs that fuel pro-tumorigenic mo-macs. We show that lung tumors prime accessibility for Nfe2l2 (NRF2) in BM myeloid progenitors as a cytoprotective response to oxidative stress, enhancing myelopoiesis while dampening interferon response and promoting immunosuppression. NRF2 activity is amplified during monocyte differentiation into mo-macs in the TME to regulate oxidative stress and drive immunosuppressive phenotype. NRF2 genetic deletion and pharmacological inhibition significantly reduced mo-macs’ survival and immunosuppression in the TME, restoring NK and T cell antitumor immunity and enhancing checkpoint blockade efficacy. Our findings identify a targetable epigenetic node of myeloid progenitor dysregulation that sustains immunoregulatory mo-macs in the lung TME, highlighting the potential of early interventions to reprogram macrophage fate for improved immunotherapy outcomes.
2025-07-07 | GSE270148 | GEO
Project description:Monocyte–derived macrophages (mo-macs) drive immunosuppression in the tumor microenvironment (TME) and tumor-enhanced myelopoiesis in the bone marrow (BM) fuels these populations. Here, we performed paired transcriptome and chromatin accessibility analysis of BM myeloid progenitors, monocytes, and tumor-infiltrating mo-macs in mice and in patients with lung cancer to identify myeloid progenitor programs that fuel pro-tumorigenic mo-macs. We show that tumors prime accessibility for Nfe2l2 (NRF2) in myeloid progenitors as a cytoprotective response to oxidative stress. NRF2 activity is sustained and increases during monocyte differentiation in the TME to regulate mo-mac stress response, in turn promoting mo-mac survival and suppressive function. NRF2 genetic deletion and pharmacological inhibition significantly reduced mo-macs’ survival and suppressive programs in the TME, enabling NK and T cell therapeutic antitumor immunity. Altogether, our study identifies a druggable epigenetic node of myeloid progenitor dysregulation that sustains immunosuppressive mo-macs in the TME.
2025-07-07 | GSE289708 | GEO
Project description:Monocyte–derived macrophages (mo-macs) drive immunosuppression in the tumor microenvironment (TME) and tumor-enhanced myelopoiesis in the bone marrow (BM) fuels these populations. Here, we performed paired transcriptome and chromatin analysis over the continuum of BM myeloid progenitors, circulating monocytes, and tumor-infiltrating mo-macs in mice and in patients with lung cancer to identify myeloid progenitor programs that fuel pro-tumorigenic mo-macs. Analyzing chromatin accessibility and histone mark changes, we show that lung tumors prime accessibility for Nfe2l2 (NRF2) in BM myeloid progenitors as a cytoprotective response to oxidative stress. NRF2 activity is sustained and increased during monocyte differentiation into mo-macs in the lung TME to regulate oxidative stress, in turn promoting metabolic adaptation, resistance to cell death, and contributing to immunosuppressive phenotype. NRF2 genetic deletion and pharmacological inhibition significantly reduced mo-macs’ survival and immunosuppression in the TME, enabling NK and T cell therapeutic antitumor immunity and synergizing with checkpoint blockade strategies. Altogether, our study identifies a targetable epigenetic node of myeloid progenitor dysregulation that sustains immunoregulatory mo-macs in the TME.
2025-07-07 | GSE255330 | GEO
Project description:Monocyte–derived macrophages (mo-macs) drive immunosuppression in the tumor microenvironment (TME) and tumor-enhanced myelopoiesis in the bone marrow (BM) fuels these populations. Here, we performed paired transcriptome and chromatin analysis over the continuum of BM myeloid progenitors, circulating monocytes, and tumor-infiltrating mo-macs in mice and in patients with lung cancer to identify myeloid progenitor programs that fuel pro-tumorigenic mo-macs. Analyzing chromatin accessibility and histone mark changes, we show that lung tumors prime accessibility for Nfe2l2 (NRF2) in BM myeloid progenitors as a cytoprotective response to oxidative stress. NRF2 activity is sustained and increased during monocyte differentiation into mo-macs in the lung TME to regulate oxidative stress, in turn promoting metabolic adaptation, resistance to cell death, and contributing to immunosuppressive phenotype. NRF2 genetic deletion and pharmacological inhibition significantly reduced mo-macs’ survival and immunosuppression in the TME, enabling NK and T cell therapeutic antitumor immunity and synergizing with checkpoint blockade strategies. Altogether, our study identifies a targetable epigenetic node of myeloid progenitor dysregulation that sustains immunoregulatory mo-macs in the TME.
2025-07-07 | GSE270127 | GEO
Project description:Human cytomegalovirus reprograms hematopoietic progenitor cells into immunosuppressive monocyte to achieve latency
| PRJNA418309 | ENA
Project description:Immunoprecipitation of Utx followed by mass spectrometry analysis to identify Utx binding partners in mouse myeloid progenitor cells.
2018-04-30 | PXD005011 | Pride
Project description:Impaired immunity in patients with late-stage cancer is not limited to antitumor responses, as demonstrated by poor vaccination protection and high susceptibility to infection1-3. This has been largely attributed to chemotherapy-induced impairment of innate immunity, such as neutropenia2, whereas systemic effects of tumors on hematopoiesis and adoptive immunity remain incompletely understood. Here we observed anemia associated with severe deficiency of CD8+ T cell responses against pathogens in treatment-naive mice bearing large tumors. Specifically, we identify CD45+ erythroid progenitor cells (CD71+TER119+; EPCs) as robust immunosuppressors. CD45+ EPCs, induced by tumor growth-associated extramedullary hematopoiesis, accumulate in the spleen to become a major population, outnumbering regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). The CD45+ EPC transcriptome closely resembles that of MDSCs, and, like MDSCs, reactive oxygen species production is a major mechanism underlying CD45+ EPC-mediated immunosuppression. Similarly, an immunosuppressive CD45+ EPC population was detected in patients with cancer who have anemia. These findings identify a major population of immunosuppressive cells that likely contributes to the impaired T cell responses commonly observed in patients with advanced cancer.
| S-EPMC6211844 | biostudies-literature