High expression of Galectin-1 in pancreatic stellate cells plays a role in the development and maintenance of an immunosuppressive microenvironment in pancreatic cancer.

Abstract

Galectin-1 is implicated in making tumor cells immune privileged, in part by regulating the survival of infiltrating T cells. Galectin-1 is strongly expressed in activated pancreatic stellate cells (PSCs); however, whether this is linked to tumor cell immune escape in pancreatic cancer is unknown. Galectin-1 was knocked down in PSCs isolated from pancreatic tissues using small interfering RNA (siRNA), or overexpressed using recombinant lentiviruses, and the PSCs were cocultured with T cells. CD3(+) , CD4(+) and CD8(+) T cell apoptosis was detected by flow cytometry; T cell IL-2, IL-4, IL-5 and INF-γ production levels were quantified using ELISA. Immunohistochemical analysis showed increased numbers of PSCs expressed Galectin-1 (p < 0.01) and pancreatic cancers had increased CD3(+) T cell densities (p < 0.01) compared to normal pancreas or chronic pancreatitis samples. In coculture experiments, PSCs that overexpressed Galectin-1 induced apoptosis of CD4(+) T cells (p < 0.01) and CD8(+) T cells (p < 0.05) significantly, compared to normal PSCs. Knockdown of Galectin-1 in PSCs increased CD4(+) T cell (p < 0.01) and CD8(+) T cell viability (p < 0.05). Supernatants from T cells cocultured with PSCs that overexpressed Galectin-1 contained significantly increased levels of Th2 cytokines (IL-4 and IL-5, p < 0.01) and decreased Th1 cytokines (IL-2 and INF-γ, p < 0.01). However, the knockdown of PSC Galectin-1 had the opposite effect on Th1 and Th2 cytokine secretion. Our study suggests that the overexpression of Galectin-1 in PSCs induced T cell apoptosis and Th2 cytokine secretion, which may regulate PSC-dependent immunoprivilege in the pancreatic cancer microenvironment. Galectin-1 may provide a novel candidate target for pancreatic cancer immunotherapy.

• Authors: Dong Tang, Zhongxu Yuan, Xiaofeng Xue, Zipeng Lu, Ye Zhang, Hui Wang, Minyong Chen, Yong An, Jishu Wei, Yi Zhu, Yi Miao, Kuirong Jiang
• Journal: International journal of cancer (Int J Cancer) Vol. 130 Issue 10 Pg. 2337-48 (May 15 2012) ISSN: 1097-0215 [Electronic] United States
• PMID: 21780106 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 UICC.

Chemical References

• CD3 Complex
• Galectin 1
• Interleukins

Topics

• Adult
• Aged
• Aged, 80 and over
• CD3 Complex (metabolism)
• Female
• Galectin 1 (genetics, metabolism)
• Gene Knockdown Techniques
• Humans
• Interleukins (metabolism)
• Male
• Middle Aged
• Pancreatic Neoplasms (immunology, metabolism)
• Pancreatic Stellate Cells (immunology, metabolism)
• T-Lymphocytes (metabolism)
• Tumor Escape
• Tumor Microenvironment (immunology)