Low-dose cyclophosphamide modulates galectin-1 expression and function in an experimental rat lymphoma model.
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.
Zacarías Fluck
Mariano F
MF
Institute of Experimental Genetics, School of Medical Sciences, National University of Rosario, Santa Fe 3100, 2000 Rosario, Argentina.
Rico
María J
MJ
Gervasoni
Silvia I
SI
Ilarregui
Juan M
JM
Toscano
Marta A
MA
Rabinovich
Gabriel A
GA
Scharovsky
O Graciela
OG
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D003520:Cyclophosphamide / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D037483:Galectin 1 / Q000096:biosynthesis / Q000187:drug effects*; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis / Q000473:pathology; D008223:Lymphoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D018906:Antineoplastic Agents, Alkylating; D037483:Galectin 1; D003520:Cyclophosphamide