In recent years, one of the most important insights into
tumor immunity was provided by the identification of negative regulatory pathways and immune escape strategies that greatly influence the magnitude of antitumor responses.
Galectin-1 (Gal-1), a member of a family of highly conserved
beta-galactoside-
binding proteins, has been recently shown to contribute to
tumor cell evasion of immune responses by modulating survival and differentiation of effector T cells. However, there is still scarce information about the regulation of
Gal-1 expression and function in vivo. Here we show that administration of a single low-dose
cyclophosphamide (Cy), which is capable of restraining
metastasis in the rat
lymphoma model L-
TACB, can also influence
Gal-1 expression in primary
tumor,
metastasis, and spleen cells and modulate the effects of this
protein on T cell survival. A time-course study revealed a positive correlation between
Gal-1 expression and
tumor volume in primary
tumor cells. Conversely,
Gal-1 expression was significantly reduced in spleen cells and
lymph node metastasis throughout the period studied. Interestingly,
cyclophosphamide treatment was capable of restoring the basal levels of
Gal-1 expression in primary
tumors and spleens. In addition, this antimetastatic agent rendered spleen T cells from
tumor-bearing animals resistant to Gal-1-induced cell death. Our results suggest that, in addition to other well-known functions of
cyclophosphamide, this immunomodulatory agent may also modulate
Gal-1 expression and function during
tumor growth and
metastasis with critical implications for tumor-immune escape and
immunotherapy.