ArticleCell death & disease2026
Sphingosine-1-phosphate promotes CD8 T cell exhaustion in breast cancer via exosomal transfer of TGFBR2.
Article in Cell death & disease, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
2 citing papers in PubMed.
- Post-Translational Modifications in Cancer-Associated CD8⁺ T-Cell Exhaustion: Mechanisms and Therapeutic Opportunities.International journal of biological sciences · 2026Review
- Glioma-derived extracellular vesicles as drivers of immunotherapeutic resistance: mechanisms of immune reprogramming and metabolic intervention.Frontiers in immunology · 2026Review
Corrections and comments
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sphingosine-1-phosphate (S1P) has been implicated in promoting breast cancer progression, but its role in fostering an immunosuppressive microenvironment remains largely unexplored. In our study, co-culturing CD8 T cells with S1P-treated MCF7 cells significantly reduced CD8 T cell proliferation, an effect reversed by inhibiting exosome biogenesis. S1P treatment enhanced exosome release from breast cancer cells, with increased levels of TGFBR2 detected on the exosome surface. These S1P-induced exosomes promoted CD8 T cell exhaustion. Silencing TGFBR2 in cancer cells or treating with anti-TGFBR2 antibodies mitigated CD8 T cell exhaustion thereby highlighting the pivotal role of TGFBR2. Further investigation revealed that S1P drives the production of TGFBR2-loaded exosomes by activating the S1P1 receptor and engaging the AKT-Rab27a axis to facilitate exosome release. Additionally, S1P upregulates TGFBR2 expression and stability through the S1P1-LEF1 and S1P1-CREB1-USP8 pathways respectively, thereby contributing to immune suppression. In vivo administration of exosomes derived from S1P-treated murine breast cancer cells in a breast cancer allograft model markedly promoted tumor growth and heightened CD8 T cell exhaustion, whereas exosomes from TGFBR2-silenced, S1P-treated cells exerted the reverse effect, underscoring the pivotal role of the S1P-TGFBR2 axis in modulating the tumor microenvironment. These findings suggest that targeting the S1P-TGFBR2 pathway could enhance antitumor immunity in breast cancer.
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