Apoptosis and anergy of T cell induced by pancreatic stellate cells-derived galectin-1 in pancreatic cancer.
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.
Department of General Surgery, Clinical Medical College, Yangzhou University (Subei People's Hospital of Jiangsu Province), Yangzhou, 225001, People's Republic of China.
Dong
D
Tang
Jun
J
Gao
Sen
S
Wang
Zhongxu
Z
Yuan
Nianyuan
N
Ye
Yang
Y
Chong
Chuanqi
C
Xu
Xuetong
X
Jiang
Bin
B
Li
Wei
W
Yin
Yi
Y
Miao
Daorong
D
Wang
Kuirong
K
Jiang
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D017635:Clonal Anergy / Q000235:genetics*; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D037483:Galectin 1 / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D058954:Pancreatic Stellate Cells / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D059016:Tumor Microenvironment / Q000235:genetics
D016207:Cytokines; D037483:Galectin 1