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We are analyzing https://www.nature.com/articles/s43018-020-0038-2.

Title:
Bystander IFN-γ activity promotes widespread and sustained cytokine signaling altering the tumor microenvironment | Nature Cancer
Description:
The cytokine interferon (IFN)-γ produced by tumor-reactive T cells is a key effector molecule with pleiotropic effects during anti-tumor immune responses. Although IFN-γ production is targeted at the immunologic synapse, its spatiotemporal activity within the tumor remains elusive. In the present study, we report that, although IFN-γ secretion requires local antigen recognition, IFN-γ diffuses extensively to alter the tumor microenvironment in distant areas. Using intravital imaging and a reporter for STAT1 translocation, we provide evidence that T cells mediate sustained IFN-γ signaling in remote tumor cells. Furthermore, tumor phenotypic alterations required several hours of exposure to IFN-γ, a feature that disfavored local IFN-γ activity over diffusion and bystander activity. Finally, single-cell RNA-sequencing data from melanoma patients also suggested bystander IFN-γ activity in human tumors. Thus, tumor-reactive T cells act collectively to create large cytokine fields that profoundly modify the tumor microenvironment. Two papers by Schumacher and colleagues and Bousso and colleagues show that sensing of IFN-γ by a small number of tumor cells leads to propagation of IFN-γ sensing and response across a larger fraction of the tumor.
Website Age:
30 years and 10 months (reg. 1994-08-11).

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Custom-built

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🚀🌠 Tremendous Traffic: 10M - 20M visitors per month


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Keywords {🔍}

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Topics {✒️}

nature portfolio journals permissions reprints nature portfolio privacy policy european research council tailed mann-whitney u-test single-cell rna-sequencing data advertising social media tailed unpaired t-test research pre-clinical development content carpet-bombing tumors showing ifn-γ-deficient ot nature+ nature 494 nature 569 nature 545 nature aminomethyl-4-methoxymethyl-5-hydroxy-6-methylpyridine bristol-myers squibb foundation tumor development ifn-γ-mediated inhibition antigen-expressing cellular patches ifn-γ diffuses extensively anti-ifn-γ mab putative ifn-γ concentration dimensional intact-tissue sequencing high-incidence spontaneous lymphoma cell-derived ifn-γ ebv-positive burkitt lymphoma ifn-gamma pathway genes anti-tumor immune responses tunable diffusion–consumption mechanism antigen-positive tumor cells intratumoral ifn-γ concentration ifn-γ-deficient ot single-cell transcriptional states integrative single-cell analysis mu-myc transgenic mouse permissions springerlink instant access rag2-/-γc-/- recipient mice recipient rag2-/-γc-/- mice recipient rag2−/−γc−/− mice ova-expressing eµ-myc eµ-myc cells expressing long-lived inflammation histograms showing h2-kb pd-1 immunoinhibitory receptor

Questions {❓}

  • Interferon-γ: teammate or opponent in the tumour microenvironment?

Schema {🗺️}

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      affiliation:
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            address:
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               type:PostalAddress
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            name:Institut Pasteur CNRS
            address:
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               type:PostalAddress
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            name:Sorbonne Université
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            address:
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            address:
               name:Dynamics of Immune Responses Unit, Equipe Labellisée Ligue Contre le Cancer, Institut Pasteur, INSERM U1223, Paris, France
               type:PostalAddress
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            name:University Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur
            address:
               name:University Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur, Paris, France
               type:PostalAddress
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               name:Dynamics of Immune Responses Unit, Equipe Labellisée Ligue Contre le Cancer, Institut Pasteur, INSERM U1223, Paris, France
               type:PostalAddress
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      name:Zacarias Garcia
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            name:Institut Pasteur, INSERM U1223
            address:
               name:Dynamics of Immune Responses Unit, Equipe Labellisée Ligue Contre le Cancer, Institut Pasteur, INSERM U1223, Paris, France
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      name:Ido Amit
      url:http://orcid.org/0000-0003-2968-877X
      affiliation:
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            address:
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               name:Dynamics of Immune Responses Unit, Equipe Labellisée Ligue Contre le Cancer, Institut Pasteur, INSERM U1223, Paris, France
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               type:PostalAddress
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            name:Institut Pasteur CNRS
            address:
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      name:University Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur, Paris, France
      name:Department of Immunology, Weizmann Institute of Science, Rehovot, Israel
      name:Systems Biology Group, Center for Bioinformatics, Biostatistics, and Integrative Biology and USR 3756, Institut Pasteur CNRS, Paris, France
      name:Sorbonne Université, Paris, France
      name:Dynamics of Immune Responses Unit, Equipe Labellisée Ligue Contre le Cancer, Institut Pasteur, INSERM U1223, Paris, France
      name:Dynamics of Immune Responses Unit, Equipe Labellisée Ligue Contre le Cancer, Institut Pasteur, INSERM U1223, Paris, France
      name:University Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur, Paris, France
      name:Dynamics of Immune Responses Unit, Equipe Labellisée Ligue Contre le Cancer, Institut Pasteur, INSERM U1223, Paris, France
      name:Dynamics of Immune Responses Unit, Equipe Labellisée Ligue Contre le Cancer, Institut Pasteur, INSERM U1223, Paris, France
      name:Department of Immunology, Weizmann Institute of Science, Rehovot, Israel
      name:Dynamics of Immune Responses Unit, Equipe Labellisée Ligue Contre le Cancer, Institut Pasteur, INSERM U1223, Paris, France
      name:Dynamics of Immune Responses Unit, Equipe Labellisée Ligue Contre le Cancer, Institut Pasteur, INSERM U1223, Paris, France
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