Dataset Information

Expression data from in vitro-induced non-hypoxic tumour associated macrophages (TAMs)

ABSTRACT: Active immunotherapy is a promising strategy for anti-angiogenic cancer therapy. Recently, we have reported that a vaccine using human umbilical vein endothelial cells (HUVECs) induced specific anti-endothelial immune responses in the most of immunized patients, and resulted in tumor regression in some patients with recurrent malignant brain tumors, whereas not in colorectal cancer patients. In this study, we hypothesized that non-hypoxic perivascular tumor associated macrophages (TAMs) in colorectal cancer, but not in glioblastoma, might negatively alter the therapeutic efficacy of anti-angiogenic active immunotherapy. To test this hypothesis, we examined global gene expression profiles of non-hypoxic macrophages stimulated in vitro by soluble factors released from tumor cells of human glioblastoma U-87MG (‘brain TAMs’) or colorectal adenocarcinoma HT-29 (‘colon TAMs’).

ORGANISM(S): Mus musculus

PROVIDER: GSE18804 | GEO | 2012/04/01

SECONDARY ACCESSION(S): PRJNA121217

REPOSITORIES: GEO

ACCESS DATA

Similar Datasets

Project description:Tumor hypoxia is linked to poor outcome for many cancers, but the underlying mechanisms and the environmental factors that initiate tumor hypoxia are poorly understood. Here, we tracked tumor hypoxia in glioblastoma (GBM), a highly malignant brain cancer, in immunocompetent mice with a sensitive fluorescent reporter combined with single cell transcriptomics. We found that hypoxic GBM cells are quiescent and display a mesenchymal transition, both linked to malignant potency. We also captured in vivo hypoxia gene signature, which is more represented in recurrent GBM and predicts worse outcome. Interestingly, hypoxic GBM cells is a diverse population, consisted of four subclusters, and enriched for immune pathways. Concordantly, our reporter highlighted a distinct geographic pattern of immune cells in hypoxic regions, with phagocytic tumor-associated macrophages (TAMs) and CD8+ cytotoxic T cells (CTLs) congregated in hypoxic cores confined by hypoxic GBM cells in pseudopalisading patterns. Mechanistically, this is a dynamic temporospatial process, requiring cytokine CCL8. Remarkably, the sequestered TAMs also experience hypoxia, and they are reprogrammed to an immunotolerant state by factors released from hypoxic GBM cells. Contrary to the conventional viewpoint that hypoxia arises from rapid tumor expansion outstripping vascular supply, we discovered anticancer immunity as an important driving force of tumor hypoxia. Attenuating immune responses by implanting GBM in host mice with immunodeficiency or IL1β deletion significantly decreased GBM hypoxia in well-established tumors. Unexpectedly, radiation therapy (XRT) greatly reduced tumor hypoxia, and when combined with evofosfamide, a prodrug activated by hypoxia, achieved enhanced efficacy in tumor shrinkage and eradication of hypoxic GBM population. Analyses of human patient GBM samples highlighted a connection of mesenchymal subtype, immune response, and tumor hypoxia, all contributing to poor survival. Altogether, our study revealed a reciprocal influence of anti-tumor immunity and tumor hypoxia, which has important ramification for prognosis and immunotherapy for GBM.

Dataset Information

Expression data from in vitro-induced non-hypoxic tumour associated macrophages (TAMs)

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure