title: Galectins and their ligands: negative regulators of anti-tumor immunity.
abstract: Cytotoxic CD8(+) T cells are major players of anti-tumor immune responses, as their functional activity can limit tumor growth and progression. Data show that cytotoxic T cells efficiently control the proliferation of tumor cells through major histocompatibility complex class I-mediated mechanisms; nevertheless, the presence of tumor-infiltrating CD8(+) T cells in lesional tissue does not always correlate with better prognosis and increased survival of cancer patients. Similarly, adoptive transfer of tumor-specific cytotoxic T cells has only shown marginal improvement in life spans of patients with metastatic disease. In this report, we discuss experimental evidence showing that expression of tumor-derived galectins, galectin (Gal)-1, Gal-3 and Gal-9, and concomitant presence of their ligands on the surface of anti-tumor immunocytes directly compromise anti-tumor CD8(+) T cell immune responses and, perhaps, undermine the promise of adoptive CD8(+) T cell immunotherapy. Furthermore, we describe novel strategies designed to counteract Gal-1-, Gal-3- and Gal-9-mediated effects and highlight their targeting potential for creating more effective anti-tumor immune responses. We believe that Gal and their ligands represent an efficacious targeted molecular paradigm that warrants clinical evaluation.
authors.affiliation: Department of Dermatology, Brigham and Women's Hospital, HIM, Boston, MA 02115, USA.
authors.forename: Filiberto
authors.initials: F
authors.lastname: Cedeno-Laurent
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Dimitroff
mesh_terms: D000818:Animals; D003602:Cytotoxicity, Immunologic; D037161:Galectins / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019139:Tumor Escape
chemical_list: D037161:Galectins; D008024:Ligands