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T-cell dysfunction in the glioblastoma microenvironment is mediated by myeloid cells releasing interleukin-10.

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 dr

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T-cell dysfunction in the glioblastoma microenvironment is mediated by myeloid cells releasing interleukin-10.

> 商业许可源文 · EUROPE_PMC · [CC-BY](https://creativecommons.org/licenses/by/)

书目信息

  • 引用：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, Bengsch B, Schnell O, Heiland DH. (2022). T-cell dysfunction in the glioblastoma microenvironment is mediated by myeloid cells releasing interleukin-10. Nature communications. PMID 35177622 · PMC8854421 · DOI 10.1038/s41467-022-28523-1
  • 证据类型：PRIMARY_RESEARCH
  • 主题：single-cell
  • 被引次数（采集时）：292
  • 原始记录：[Europe PMC](https://europepmc.org/article/MED/35177622)
  • 来源许可：[CC-BY](https://creativecommons.org/licenses/by/)

    • 作者摘要（按来源许可复用）

    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.

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    T-cell dysfunction in the glioblastoma microenvironment is mediated by myeloid cells releasing interleukin-10. · GeniOmics