Sphingosine-1-phosphate promotes CD8 T cell exhaustion in breast cancer via exosomal transfer of TGFBR2 - PubMed
3 hours ago
- #S1P-TGFBR2 pathway
- #breast cancer
- #CD8 T cell exhaustion
- Sphingosine-1-phosphate (S1P) promotes CD8 T cell exhaustion in breast cancer via exosomal transfer of TGFBR2.
- S1P-treated MCF7 cells reduce CD8 T cell proliferation, reversed by inhibiting exosome biogenesis.
- S1P enhances exosome release from breast cancer cells, increasing TGFBR2 levels on exosome surfaces.
- S1P-induced exosomes promote CD8 T cell exhaustion, mitigated by silencing TGFBR2 or using anti-TGFBR2 antibodies.
- S1P activates the S1P1 receptor and the AKT-Rab27a axis to produce TGFBR2-loaded exosomes.
- S1P upregulates TGFBR2 expression and stability via S1P1-LEF1 and S1P1-CREB1-USP8 pathways, contributing to immune suppression.
- In vivo, exosomes from S1P-treated breast cancer cells promote tumor growth and CD8 T cell exhaustion, reversed by TGFBR2 silencing.
- Targeting the S1P-TGFBR2 pathway could enhance antitumor immunity in breast cancer.