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. EV-TβRII delivered as a cargo to CD8+ T cells induces the activation of SMAD3, which is associated and cooperated with TCF1 transcription factor to impose CD8+ T cell exhaustion. Here, SMAD3 is linked to breast cancer.