Defining the Fate and Function of Effector T cells Through Galectin-1–Galectin-1 Ligand-Binding Interactions: Implications in Tumor Immunity

Abstract

Galectin-1 (Gal-1), a member of an ancient family of animal glycan-binding proteins, has been implicated in a variety of biological events. Interactions between Gal-1 and Gal-1 ligands on T cells are critically involved in regulating the nature and intensity of T-cell-mediated inflammation and antitumor immunity. Appropriately glycosylated T-cell-membrane glycoconjugates operationally defined as Gal-1 ligands bind Gal-1 and elicit downstream cellular activities that dampen effector T-cell function. Together, these biological constituents represent promising targets in the development of novel anti-inflammatory and antitumor immune therapies. Whether through characteristic elevations in tumor-derived Gal-1 or an imbalance in regulatory and Gal-1 ligand+ effector T-cell subsets during inflammation, the Gal-1–Gal-1 ligand-binding axis offers numerous cellular/tissue contexts to strategically interfere with Gal-1 efficacy. In this chapter, we will examine recent assessments of (1) Gal-1 expression and function in controlling both adaptive and antitumor T-cell immunity, (2) identity and function of T-cell Gal-1 ligands, and (3) targeting of the Gal-1–Gal-1 ligand axis to regulate inflammation or boost antitumor immune responses. These research disciplines collectively highlight the importance of understanding the identity and functional nature of Gal-1 and its ligands to strategically and safely manipulate the immune system to control immunopathologic conditions.