Bystander Ifn-Gamma Activity Promotes Widespread And Sustained Cytokine Signaling Altering The Tumor Microenvironment
NATURE CANCER(2020)
摘要
The cytokine interferon (IFN)-gamma produced by tumor-reactive T cells is a key effector molecule with pleiotropic effects during anti-tumor immune responses. Although IFN-gamma production is targeted at the immunologic synapse, its spatiotemporal activity within the tumor remains elusive. In the present study, we report that, although IFN-gamma secretion requires local antigen recognition, IFN-gamma 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-gamma signaling in remote tumor cells. Furthermore, tumor phenotypic alterations required several hours of exposure to IFN-gamma, a feature that disfavored local IFN-gamma activity over diffusion and bystander activity. Finally, single-cell RNA-sequencing data from melanoma patients also suggested bystander IFN-gamma 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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关键词
Imaging the immune system,Tumour immunology,Life Sciences,general
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