Exosomal TGF-β1 is correlated with lymphatic metastasis of gastric cancers

Exosomes are nano-vesicles transporting bioactive material between cells. This study explored the prognostic association of exosomal TGF-β1 with lymph node (LN) metastasis of gastric cancer (GC). TGF-β1 expressions in the exosomes isolated from the gastroepiploic veins of 61 GC patients analyzed by ELISA. The regulatory T (Treg) cells in celiac LNs of gastric cancer analyzed by immunohistochemistry. Exosomal TGF-β1 expression and the ratio of Treg cells in draining LNs were both significantly associated with pathological stages and LN metastasis of gastric cancer. Besides, the exosomal TGF-β1 expression and Treg proportion in LN were also significantly correlated in gastric cancer patients. Recombinant TGF-β1 and exosomes isolated from GC patients were used to induce FOXP3⁺ Treg cells from naïve T cells in vitro. Compared to the control, recombinant TGF-β1 induced more CD25 (41%), FOXP3 (19%) and CTLA-4 (47%), while reduced CD45RA expression by 38% in primary naïve T cell cultures (p<0.01). Exosomes treatment induced more CD25 and 45% higher CTLA-4 expression, and increased 29% higher of CD45RA-negative cells than recombinant TGF-β1 did (p<0.01). Adding TGF-β1 neutralizing antibody partially abrogated the effects of exosomes on Treg induction. Our study showed exosomal TGF-β1 related to lymph node metastasis and the ratio of Treg cells in lymph nodes of gastric cancers. Exosomes from gastric cancer patients could induce Treg cells formation through the effect of TGF-β1.