Galectin-9 - ligand axis: an emerging therapeutic target for multiple myeloma

Front Immunol. 2024 Sep 25:15:1469794. doi: 10.3389/fimmu.2024.1469794. eCollection 2024.

Abstract

Galectin-9 (Gal-9) is a tandem-repeat galectin with diverse roles in immune homeostasis, inflammation, malignancy, and autoimmune diseases. In cancer, Gal-9 displays variable expression patterns across different tumor types. Its interactions with multiple binding partners, both intracellularly and extracellularly, influence key cellular processes, including immune cell modulation and tumor microenvironment dynamics. Notably, Gal-9 binding to cell-specific glycoconjugate ligands has been implicated in both promoting and suppressing tumor progression. Here, we provide insights into Gal-9 and its involvement in immune homeostasis and cancer biology with an emphasis on multiple myeloma (MM) pathophysiology, highlighting its complex and context-dependent dual functions as a pro- and anti-tumorigenic molecule and its potential implications for therapy in MM patients.

Keywords: galectin-9; galectins; multiple myeloma; therapy; tumor microenvironment.

Publication types

  • Review

MeSH terms

  • Animals
  • Galectins* / immunology
  • Galectins* / metabolism
  • Humans
  • Ligands
  • Molecular Targeted Therapy
  • Multiple Myeloma* / drug therapy
  • Multiple Myeloma* / immunology
  • Multiple Myeloma* / metabolism
  • Multiple Myeloma* / therapy
  • Signal Transduction
  • Tumor Microenvironment* / immunology

Substances

  • Galectins
  • LGALS9 protein, human
  • Ligands

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This review was supported by the NIH/National Cancer Institute (NCI) Alliance of Glycobiologists for Cancer Research: Biological Tumor Glycomics Laboratory U01 grant CA225644 (CD) and NIH/NCI R01 grant CA282520 (CD).