Apoptosis and anergy of T cell induced by pancreatic stellate cells-derived galectin-1 in pancreatic cancer.

Abstract

Galectin-1, a β-galactoside-binding protein implicated in cancer cell immune privilege, was highly expressed in activated pancreatic stellate cells (PSCs). This study was designed to investigate the relationship between PSC-derived galectin-1 and tumor immunity in pancreatic cancer. Isolated PSCs were identified as normal pancreas cells (hNPSCs) or pancreatic cancer cells (hCaPSCs) by immunohistochemical staining for α-SMA and vimentin, and galectin-1 expression was evaluated by Western blotting and quantitative RT-PCR. Apoptosis, caspase activity, and cytokine production (IL-6, IL-10, TNF-β, and IFN-γ) of T cells co-cultured with PSCs were evaluated, and immunohistochemical staining of galectin-1 was correlated with CD3 and clinicopathological variables in 66 pancreatic cancer and 10 normal pancreatic tissue samples. hCaPSCs exhibited higher galectin-1 expression than did hNPSCs, and hCaPSCs induced higher levels of apoptosis in T cells following co-culture. hCaPSCs activated caspase-9 and caspase-3 in the mitochondrial apoptotic pathway and stimulated secretion of Th2 cytokines (IL-6 and IL-10) but decreased secretion of Th1 cytokines (TNF-β and IFN-γ), compared with hNPSCs. Immunohistochemical staining indicated that galectin-1 and CD3 were more highly expressed in pancreatic cancer tissue. Galectin-1 expression was highest in poorly differentiated pancreatic cancer cells and lowest in well-differentiated pancreatic cancer cells and was associated with tumor size, lymph node metastasis, differentiation, and UICC stage. However, CD3 expression showed the opposite trend and was highest in well-differentiated pancreatic cancer cells and was associated with tumor differentiation and UICC stage. High expression of galectin-1 was associated with short survival, as was low expression of CD3. hCaPSC-derived galectin-1 enhanced apoptosis and anergy of T cells in pancreatic cancer, which contributes to the immune escape of pancreatic cancer cells.

• Authors: Dong Tang, Jun Gao, Sen Wang, Zhongxu Yuan, Nianyuan Ye, Yang Chong, Chuanqi Xu, Xuetong Jiang, Bin Li, Wei Yin, Yi Miao, Daorong Wang, Kuirong Jiang
• Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) Vol. 36 Issue 7 Pg. 5617-26 (Jul 2015) ISSN: 1423-0380 [Electronic] Netherlands
• PMID: 25725585 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Galectin 1

Topics

• Adult
• Aged
• Apoptosis (genetics)
• Cell Differentiation (genetics)
• Cell Proliferation (genetics)
• Clonal Anergy (genetics)
• Cytokines (biosynthesis)
• Female
• Galectin 1 (biosynthesis, genetics)
• Gene Expression Regulation, Neoplastic
• Humans
• Male
• Middle Aged
• Pancreatic Neoplasms (genetics, immunology, pathology)
• Pancreatic Stellate Cells (pathology)
• T-Lymphocytes (immunology, pathology)
• Tumor Microenvironment (genetics)