Galectin-1 (Gal-1) has been described to promote
tumor growth by inducing angiogenesis and to contribute to tumor immune escape by promoting apoptosis of activated T cells. We had previously identified upregulation of
Gal-1 in preclinical models of aggressive
neuroblastoma (NB), a solid
tumor of childhood. However, the clinical and
biological relevance of
Gal-1 in this
tumor entity is unclear. Here, the effect of
Gal-1 on the immune system and
tumorigenesis was assessed using modulation of
Gal-1 expression in immune effector cells and in a transgenic NB model, designated TH-MYCN. The fraction of CD4(+) T cells was decreased in
tumor-bearing TH-MYCN mice compared to
tumor-free littermates, while both CD4(+) T cells as well as CD8(+) T cells were less activated, compatible with a reduced immune response in
tumor-bearing mice.
Tumor incidence was not significantly altered by decreasing
Gal-1/
LGALS1 gene dosage in TH-MYCN mice, but TH-MYCN/
Gal-1(-/-) double transgenic mice displayed impaired
tumor angiogenesis,
splenomegaly, and impaired T cell
tumor-infiltration with no differences in T cell activation and apoptosis rate. Additionally, a lower migratory capacity of
Gal-1 deficient CD4(+) T cells toward
tumor cells was observed in vitro.
Transplantation of TH-MYCN-derived
tumor cells into syngeneic mice resulted in significantly reduced
tumor growth and elevated immune cell infiltration when
Gal-1 was downregulated by
shRNA. We therefore conclude that T cell-derived
Gal-1 mediates T cell
tumor-infiltration, whereas NB-derived
Gal-1 promotes
tumor growth. This opposing effect of
Gal-1 in NB should be considered in therapeutic targeting strategies, as currently being developed for other
tumor entities.