Breast cancer cell-derived extracellular vesicles promote CD8⁺ T cell exhaustion via TGF-β type II receptor signaling.

ABSTRACT: Cancer immunotherapies have shown clinical success in various types of tumors but the patient response rate is low, particularly in breast cancer. Here we report that malignant breast cancer cells can transfer active TGF-β type II receptor (TβRII) via tumor-derived extracellular vesicles (TEV) and thereby stimulate TGF-β signaling in recipient cells. Up-take of extracellular vesicle-TβRII (EV-TβRII) in low-grade tumor cells initiates epithelial-to-mesenchymal transition (EMT), thus reinforcing cancer stemness and increasing metastasis in intracardial xenograft and orthotopic transplantation models. EV-TβRII delivered as cargo to CD8⁺ T cells induces the activation of SMAD3 which we demonstrated to associate and cooperate with TCF1 transcription factor to impose CD8⁺ T

SUBMITTER: Xie F 

PROVIDER: S-EPMC9343611 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature