Galectin-8 alters immune microenvironment and promotes tumor progression

  • Am J Cancer Res. 2023 Jun 15;13(6):2517-2529.
Yiting Wang  1  2 ,  Yufan Sun  3 ,  Hai Li  1 ,  Jie Xu  2
Affiliations
  • 1. Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai, China.
  • 2. Institutes of Biomedical Sciences, Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Fudan University Shanghai, China.
  • 3. BioTroy Therapeutics Shanghai, China.
PMID: 37424827
Abstract

Galectin-8 (Gal-8), encoded by LGALS8 gene, is a unique member of the Galectin family with diverse biological functions, including tumor-modulating capabilities. Recently, evidence has accumulated supporting an essential role for Gal-8 in regulating innate and adaptive immunity, with high expression in Tumors and other immune dysregulation diseases. This study reveals the role of Gal-8-induced tumor Immunosuppression by analyzing animal models and clinical data of tumor-infiltrating cells. In Gal-8 expressing tumor, we found that suppressive immune cells, including Tregs and MDSCs, expanded while CD8+ cells decreased, providing direct evidence that Gal-8 regulates the tumor immune microenvironment. In addition, we not only analyzed the expression of Gal-8 in clinical samples of breast and Colorectal Cancer but also classified the tissue expression patterns. Further analysis revealed that Gal-8 correlates with lymph node metastasis and immunophenotyping. Consistent with animal experiments, our analysis of LGALS8 gene expression showed its negative association with infiltrated active CD8+ T cells and immune stimulatory modulators in cancers. Our study identified the potential prognostic and therapeutic value of Gal-8, and further research on developing corresponding targeted therapeutic strategies is awaited.

Keywords
Galectin-8; Tumor microenvironment; breast cancer; colorectal cancer; prognosis.
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