Programmed death ligand-1 and galectin-1: pieces in the puzzle of tumor-immune escape

Abstract

Despite major advances in the understanding of tumor rejection mechanisms, the successful translation of basic and preclinical information into an effective tumor immunotherapy in the clinic has continued to falter. It has become increasingly apparent that one important obstacle is the activation of immunosuppressive mechanisms and inhibitory pathways that act in concert to thwart immune effector responses. This chapter discusses biochemical and functional aspects of two inhibitory signals, stimulated by the cellular ligands programmed death ligand 1 (PDL-1) and galectin 1, that help create an immunosuppressive network in the tumor microenvironment. Evidence is mounting that these inhibitory signals can infl uence tumor progression by modulating the activation, differentiation, and survival of effector T cells. Further investigation into their roles in the induction and maintenance of immune tolerance to tumor antigens may reveal appropriate frameworks to develop strategies for overcoming these barriers for cancer immunotherapy.