Abstract

Galectin-1 is implicated in making tumorcells immune privileged, in part by regulating the survival of infiltrating Tcells. Galectin-1 is strongly expressed in activated pancreatic stellate cells(PSCs); however, whether this is linked to tumor cell immune escape inpancreatic cancer is unknown. Galectin-1 was knocked down in PSCs isolated frompancreatic tissues using small interfering RNA (siRNA), or overexpressed using recombinantlentiviruses, and the PSCs were cocultured with T cells. CD3(+) , CD4(+) andCD8(+) T cell apoptosis was detected by flow cytometry; T cell IL-2, IL-4, IL-5and INF-γ production levels were quantified using ELISA. Immunohistochemicalanalysis 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 cocultureexperiments, PSCs that overexpressed Galectin-1 induced apoptosis of CD4(+) Tcells (p < 0.01) and CD8(+) T cells (p < 0.05) significantly, compared tonormal 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 coculturedwith PSCs that overexpressed Galectin-1 contained significantly increasedlevels of Th2 cytokines (IL-4 and IL-5, p < 0.01) and decreased Th1cytokines (IL-2 and INF-γ, p < 0.01). However, the knockdown of PSCGalectin-1 had the opposite effect on Th1 and Th2 cytokine secretion. Our studysuggests that the overexpression of Galectin-1 in PSCs induced T cell apoptosisand Th2 cytokine secretion, which may regulate PSC-dependent immunoprivilege inthe pancreatic cancer microenvironment. Galectin-1 may provide a novelcandidate target for pancreatic cancer immunotherapy.