title: 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.affiliation: Department of General Surgery, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Dong
authors.initials: D
authors.lastname: Tang
authors.forename: Zhongxu
authors.initials: Z
authors.lastname: Yuan
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Xue
authors.forename: Zipeng
authors.initials: Z
authors.lastname: Lu
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Minyong
authors.initials: M
authors.lastname: Chen
authors.forename: Yong
authors.initials: Y
authors.lastname: An
authors.forename: Jishu
authors.initials: J
authors.lastname: Wei
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhu
authors.forename: Yi
authors.initials: Y
authors.lastname: Miao
authors.forename: Kuirong
authors.initials: K
authors.lastname: Jiang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017252:CD3 Complex / Q000378:metabolism; D005260:Female; D037483:Galectin 1 / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D007378:Interleukins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000276:immunology* / Q000378:metabolism*; D058954:Pancreatic Stellate Cells / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism; D019139:Tumor Escape; D059016:Tumor Microenvironment / Q000276:immunology
chemical_list: D017252:CD3 Complex; D037483:Galectin 1; D007378:Interleukins