TARGETED INHIBITION OF GALECTIN-1 GENE EXPRESSION IN TUMOR CELLS RESULTS IN HEIGHTENED T-CELL MEDIATED REJECTION: A POTENTIAL MECHANISM OF TUMOR-IMMUNE PRIVILEGE

NATALIA RUBINSTEIN,; MARIANO ALVAREZ,; NORBERTO W. ZWIRNER,; MARTA A. TOSCANO,; JUAN M. ILARREGUI,; ALICIA BRAVO,; JOSÉ MORDOH,; LEONARDO FAINBOIM,; OSVALDO L. PODHAJCER,; GABRIEL A. RABINOVICH

CANCER CELL

Cell Press

Lugar: Boston; Año: 2004 vol. 5 p. 241 - 251

1535-6108

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.