2. Academic Validation
  3. Galectin-4 potentiates CD8+ T cell immunity by enhancing MHC-I expression on dendritic cells

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

  • Mol Ther. 2025 Aug 6;33(8):3662-3679. doi: 10.1016/j.ymthe.2025.06.040.
In-Gu Lee 1,  Jeonghyeon Lee 1,  Hyeong-Rae Kim 1,  Younghyun Lim 1,  Hye-Won Yu 2,  Tae-Hyung Kim 3,  Bumsuk Hahm 4,  Hyun Ah Kang 1,  So-Hee Hong 5,  Young-Jin Seo 6
Affiliations

Affiliations

  • 1 Department of Life Science, Chung-Ang University, 84 Heukseok-ro, Dongjak-gu, Seoul 06974, Republic of Korea.
  • 2 Department of Microbiology, College of Medicine, Ewha Womans University, 25 Magokdong-ro 2-gil, Gangseo-gu, Seoul 07804, Republic of Korea.
  • 3 Department of Pathology, School of Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.
  • 4 Departments of Surgery and Molecular Microbiology and Immunology, University of Missouri, Columbia, MO 65212, USA.
  • 5 Department of Microbiology, College of Medicine, Ewha Womans University, 25 Magokdong-ro 2-gil, Gangseo-gu, Seoul 07804, Republic of Korea. Electronic address: [email protected].
  • 6 Department of Life Science, Chung-Ang University, 84 Heukseok-ro, Dongjak-gu, Seoul 06974, Republic of Korea. Electronic address: [email protected].
PMID: 40589087 DOI: 10.1016/j.ymthe.2025.06.040
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.

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