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

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Tumor-Induced Immune Suppression

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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.

This work was supported in part by the National Institutes of Health/National Center for Complementary and Alternative Medicine grant, RO1 AT004268 (C. Dimitroff), National Institutes of Health/National Cancer Institute, RO1 CA 173610 (C. Dimitroff), and grants from Agencia Nacional de Promoción Científica y Tecnológica (Argentina), Fundación Sales (Argentina), and The National Multiple Sclerosis Society (USA) (G.A. Rabinovich).

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Authors and Affiliations

  1. Department of Dermatology, Brigham and Women’s Hospital, Harvard Medical School, HIM, Rm. 662, 77 Avenue Louis Pasteur, 02115, Boston, MA, USA

    Charles J. Dimitroff

  2. Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas de Argentina, Vuelta de Obligado 2490, C1428ADN, Buenos Aires, Argentina

    Gabriel A. Rabinovich

  3. Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, C1428ADN, Buenos Aires, Argentina

    Gabriel A. Rabinovich

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  1. Charles J. Dimitroff
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Correspondence to Gabriel A. Rabinovich .

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  1. Translational Tumor Immunology, The Wistar Institute, Philadelphia, Pennsylvania, USA

    Dmitry I. Gabrilovich

  2. N Potomac, Maryland, USA

    Arthur Andrew Hurwitz

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Dimitroff, C., Rabinovich, G. (2014). Defining the Fate and Function of Effector T cells Through Galectin-1–Galectin-1 Ligand-Binding Interactions: Implications in Tumor Immunity. In: Gabrilovich, D., Hurwitz, A. (eds) Tumor-Induced Immune Suppression. Springer, New York, NY. https://doi.org/10.1007/978-1-4899-8056-4_12

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