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Article Dans Une Revue Nature Cancer Année : 2020

Bystander IFN-γ activity promotes widespread and sustained cytokine signaling altering the tumor microenvironment

Résumé

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.
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Dates et versions

hal-02930398 , version 1 (15-10-2020)

Identifiants

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Ronan Thibaut, Pierre Bost, Idan Milo, Marine Cazaux, Fabrice Lemaître, et al.. Bystander IFN-γ activity promotes widespread and sustained cytokine signaling altering the tumor microenvironment. Nature Cancer, 2020, 1 (3), pp.302-314. ⟨10.1038/s43018-020-0038-2⟩. ⟨hal-02930398⟩
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