Galectin-4 potentiates CD8+ T cell immunity by enhancing MHC-I expression on dendritic cells

Abstract

Galectin-4 (Gal-4), a member of the β-galactoside-binding galectin family, plays a role in various physiological processes, including tumor progression and intestinal disorders. However, its contribution to adaptive immunity remains poorly understood. In this study, Gal-4 is identified as a critical factor for effective generation of CD8+ T cell responses against tumors and viral infections. Gal-4-deficient mice exhibit significantly enhanced tumor growth in syngeneic mouse cancer models, attributed to impaired CD8+ T cell responses. Similarly, antiviral CD8+ T cell responses against lymphocytic choriomeningitis virus (LCMV) are profoundly diminished in Gal-4-deficient mice. This is not due to CD8+ T cell-intrinsic defects but instead linked to decreased surface expression of antigen-MHC-I complexes on dendritic cells. Building on these findings, the therapeutic potential of Gal-4 is investigated. Administration of Gal-4 enhances the efficacy of cancer vaccines and PD-1 blockade cancer therapy to improve outcomes in tumor-bearing mice. Additionally, systemic administration of Gal-4 markedly amplifies antiviral CD8+ T cell responses against LCMV. Collectively, these results underscore the pivotal role of Gal-4 in modulating CD8+ T cell immunity and highlight its promise as a therapeutic target for the development of novel immunotherapeutics against cancer and viral diseases.

Keywords: CD8+ T cells; antitumor immunity; antiviral immunity; dendritic cells; galectin-4.