{"id":"doi:10.1038/s41467-022-28523-1","kind":"article","title":"T-cell dysfunction in the glioblastoma microenvironment is mediated by myeloid cells releasing interleukin-10","authors":["Ravi VM","Neidert N","Will P","Joseph K","Maier JP","Kückelhaus J","Vollmer L","Goeldner JM","Behringer SP","Scherer F","Boerries M","Follo M","Weiss T","Delev D","Kernbach J","Franco P","Schallner N","Dierks C","Carro MS","Hofmann UG","Fung C","Sankowski R","Prinz M","Beck J","Salié H"],"author_count":28,"year":2022,"published":"2022-02-17","venue":"Nature communications","cited_by":313,"doi":"10.1038/s41467-022-28523-1","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/s41467-022-28523-1","archive_url":"https://space-kitty.com/papers/doi:10.1038/s41467-022-28523-1","updated":null,"pmid":"35177622","pmcid":"PMC8854421","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC8854421/pdf","abstract":"Despite recent advances in cancer immunotherapy, certain tumor types, such as Glioblastomas, are highly resistant due to their tumor microenvironment disabling the anti-tumor immune response. Here we show, by applying an in-silico multidimensional model integrating spatially resolved and single-cell gene expression data of 45,615 immune cells from 12 tumor samples, that a subset of Interleukin-10-releasing HMOX1 + myeloid cells, spatially localizing to mesenchymal-like tumor regions, drive T-cell exhaustion and thus contribute to the immunosuppressive tumor microenvironment. These findings are validated using a human ex-vivo neocortical glioblastoma model inoculated with patient derived peripheral T-cells to simulate the immune compartment. This model recapitulates the dysfunctional transformation of tumor infiltrating T-cells. Inhibition of the JAK/STAT pathway rescues T-cell functionality both in our model and in-vivo, providing further evidence of IL-10 release being an important driving force of tumor immune escape. Our results thus show that integrative modelling of single cell and spatial transcriptomics data is a valuable tool to interrogate the tumor immune microenvironment and might contribute to the development of successful immunotherapies.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"T-cell dysfunction in the glioblastoma microenvironment is mediated by myeloid cells releasing interleukin-10\" by Ravi VM, Neidert N, Will P et al., https://doi.org/10.1038/s41467-022-28523-1, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"single-cell-spatial","name":"Single-Cell & Spatial Omics","domain_slug":"biotech"}],"cited_in_dossiers":[]}