P-0032 - Apoptosis and anergy of T cell induced by pancreatic stellate cells derived Galectin-1 in pancreatic cancer
|Date||28 June 2014|
|Event||World GI 2014|
|Topics|| Basic Science
|Citation||Annals of Oncology (2014) 25 (suppl_2): ii14-ii104. 10.1093/annonc/mdu165|
D. Tang1, J. Gao1, D. Wang2
Galectin-1 is an immunoregulatory protein which was expressed in the activated pancreatic stellate cells (PSCs). This study was to investigate the relationships between PSCs derived Galectin-1 and T cells in pancreatic cancer.
Expression of Galectin-1 in fresh isolated PSCs from normal pancreas (hNPSCs) and pancreatic cancer tissues (hCaPSCs) were evaluated by western blot and quantitative RT-PCR. The apoptosis of T cells, caspase activity and T cell production (IL-6, IL-10, TNF-ß and INF-ɣ) were evaluated. Immunohistochemistry was performed in 66 pancreatic cancer and 10 normal pancreas tissues to detect the Galectin-1 and CD3 expression. The relationship between Galectin-1, CD3 and clinicopathologic variables was assessed.
Vitro co-culture experiments showed that hCaPSCs induced more apoptosis of CD3 T cells, more secretion of Th2 cytokines (IL-6 and IL-10) and less secretion of Th1 cytokines (TNF-ßand INF-ɣ), than hNPSCs did (p < 0.01). hCaPSCs derived Galectin-1 induced the apoptosis of T cells mainly by initiating caspase -9 and caspase -3 in mitochondria-mediated apoptosis pathway. Galectin-1 was higher expressed in pancreatic cancer compared to normal pancreas (P < 0.05). Galectin-1 expression was gradually increased in well, moderately, poorly differentiated pancreatic cancer (P < 0.05, separately), while the CD3 expression is decreased (P < 0.05, P < 0.01). Galectin-1 expression was associated with tumor size (p = 0.007), lymph node metastasis (p = 0.019), differentiation (p = 0.021) and UICC stage (p = 0.01). CD3 expression was associated with tumor differentiation (p = 0.009) and UICC stage (p = 0.018). Expression of Galectin-1 (p < 0.001) and CD3 (p = 0.002) were associated with short patient survival.
hCaPSCs derived Galectin-1 enhances the apoptosis and anergy of T cells in pancreatic cancer, which promotes the immuno-privilege of pancreatic cancer.