STING and IRF3 in stromal fibroblasts enable sensing of genomic stress in cancer cells to undermine oncolytic viral therapy.

ABSTRACT: Cancer-associated fibroblasts (CAFs) perform diverse roles and can modulate therapy responses¹. The inflammatory environment within tumours also influences responses to many therapies, including the efficacy of oncolytic viruses²; however, the role of CAFs in this context remains unclear. Furthermore, little is known about the cell signalling triggered by heterotypic cancer cell-fibroblast contacts and about what activates fibroblasts to express inflammatory mediators^1,3. Here, we show that direct contact between cancer cells and CAFs triggers the expression of a wide range of inflammatory modulators by fibroblasts. This is initiated following transcytosis of cytoplasm from cancer cells into fibroblasts, leading to the activation of STING and IRF3-mediated

SUBMITTER: Arwert EN 

PROVIDER: S-EPMC7611090 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature