title: Targeted inhibition of galectin-1 gene expression in tumor cells results in heightened T cell-mediated rejection; A potential mechanism of tumor-immune privilege.
abstract: Despite the existence of tumor-specific immune cells, most tumors have devised strategies to avoid immune attack. We demonstrate here that galectin-1 (Gal-1), a negative regulator of T cell activation and survival, plays a pivotal role in promoting escape from T cell-dependent immunity, thus conferring immune privilege to tumor cells. Blockade of immunosuppressive Gal-1 in vivo promotes tumor rejection and stimulates the generation of a tumor-specific T cell-mediated response in syngeneic mice, which are then able to resist subsequent challenge with wild-type Gal-1-sufficient tumors. Our data indicate that Gal-1 signaling in activated T cells constitutes an important mechanism of tumor-immune escape and that blockade of this inhibitory signal can allow for and potentiate effective immune responses against tumor cells, with profound implications for cancer immunotherapy.
authors.affiliation: Division of Immunogenetics, Hospital de Clinicas José de San Martín, Buenos Aires, Argentina.
authors.forename: Natalia
authors.initials: N
authors.lastname: Rubinstein
authors.forename: Mariano
authors.initials: M
authors.lastname: Alvarez
authors.forename: Norberto W
authors.initials: NW
authors.lastname: Zwirner
authors.forename: Marta A
authors.initials: MA
authors.lastname: Toscano
authors.forename: Juan M
authors.initials: JM
authors.lastname: Ilarregui
authors.forename: Alicia
authors.initials: A
authors.lastname: Bravo
authors.forename: José
authors.initials: J
authors.lastname: Mordoh
authors.forename: Leonardo
authors.initials: L
authors.lastname: Fainboim
authors.forename: Osvaldo L
authors.initials: OL
authors.lastname: Podhajcer
authors.forename: Gabriel A
authors.initials: GA
authors.lastname: Rabinovich
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism; D016827:CD8 Antigens / Q000276:immunology / Q000378:metabolism; D002470:Cell Survival; D037483:Galectin 1 / Q000276:immunology / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D008546:Melanoma, Experimental / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D015398:Signal Transduction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D015704:CD4 Antigens; D016827:CD8 Antigens; D037483:Galectin 1