Expression of Galectin-1 controls CD8+ T Cell Proliferation in Prostate Cancer

LAURA GIRIBALDI, LUCAS GENTILINI, DANIEL COMPAGNO, DIEGO LADERACH # & GABRIEL RABINOVICH# (#CO-ÚLTIMOS AUTORES)

Lima

Congreso; Congreso de la Sociedad Latinoamericana de Inmunologia; 2012

ALAI

Galectin-1 (Gal-1), a member of the galectin family, consists of two monomers of 14.5 kDa, interacts with poly-N-acetyl-lactosamine rich saccharides. It is present in the tumor microenvironment: in tumor cells as well as in the stroma and immune cells. Little is known about the functional role of interactions between glycans and galectins in the evolutionary process of Prostate Cancer (Pca). In previous work we studied the expression profile of galectins in cell lines and patient samples with PCa. These results revealed that Gal-1 is the family member with the highest level of expression and its expression correlates positively with the degree of disease progression. Gal-8 was expressed at significant levels but did not reveal any type of regulation. On the other hand, the expression levels of most of the other galectins (Gal-3, Gal-4, Gal-12) decreased with disease progression. Since Gal-1 is expressed in both, the tumor parenchyma, antigen presenting cells (APCs) and T lymphocytes, we explore the functional role of this endogenous lectin in each compartment in the context of a normal and tumoral microenvironment. To evaluate endogenous influence each of these cell types we decided to use the prostate cancer mouse model TRAMP-C1, which is characterized by an evolutionary process similar to the human pathology. The in vitro model we have developed allows us to assess lymphocyte activation and proliferation under conditions of Gal-1 modulation on each sub-populations. This model is based on a proliferation assay with polyclonal mitogens (ConA and anti-CD3) of CFSE-labeled T cells from Gal-1 KO or wt C57/B6 mice , in the presence of APC from wt or Gal-1 KO C57/B6 mice, under the influence or not of syngeneic tumor cells, TRAMP-C1. Modulation of endogenous Gal-1 in APCs did not affect lymphocyte proliferation, neither in normal nor in a tumor context. However, the absence of Gal◘1 on CD8 + T cells promoted a significant increase in their proliferative capacity in response to stimulation with wt APC and TRAMP-C1 tumor cells (P <0.05).These results suggest that besides the role of extracellular Gal-1 on the survival of this cell type, intrinsic expression of Gal-1 by CD8+T lymphocytes has an important influence on their proliferative responses. Furthermore, increased expression of Gal-1 in T lymphocytes generates no change in the proliferative activity of tumor cells and this effect is correlated with a ´non-permissive´ glyco-phenotype (high degree of sialylation at position á-2.6, low exposure poly-N-acetyl lactosamine and core-2-O-glycans) in both TRAMP-C1 cells and in tumor samples from patients.