Galectin-1 Induces the Production of Immune-Suppressive Cytokines in Human and Mouse T Cells

Int J Mol Sci. 2024 Nov 7;25(22):11948. doi: 10.3390/ijms252211948.

Abstract

Galectin-1 is implicated in several pro-tumourigenic mechanisms and is considered immune-suppressive. The pharmacological inhibition of galectin-1 may be beneficial in cancers in which galectin-1 is overexpressed and driving cancer progression. This study aimed to further characterise the immunosuppressive cytokines influenced by galectin-1 in in vitro immune cell cultures and an in vivo inflammatory model using a recently discovered selective inhibitor of galectin-1, GB1908. To enable a translational approach and link mouse and human pharmacology, anti-CD3/anti-CD28 stimulated T cells cultured from human whole blood and mouse spleens were compared. For in vivo studies of T cell-mediated inflammation, the concanavalin-A (Con-A) mouse model was used to induce a T lymphocyte-driven acute liver injury phenotype. The inhibition of galectin-1 with GB1908 reduced IL-17A, IFNγ and TNFα in a concentration-dependent manner in both mouse and human T cells in vitro. The immunosuppressive cytokines measured in Con-A-treated mice were all upregulated compared to naïve mice. Subsequently, mice treated with GB1908 demonstrated a significant reduction in IL-17A, IFNγ, IL-6 and TNFα compared to vehicle-treated mice. In conclusion, galectin-1 induced the production of several important immune-suppressive cytokines from T cells in vitro and in vivo. This result suggests that, in the context of cancer therapy, a selective galectin-1 could be a viable approach as a monotherapy, or in combination with chemotherapeutic agents and/or checkpoint inhibitors, to enhance the numbers and activity of cytotoxic T cells in the tumour microenvironment of high galectin-1 expressing cancers.

Keywords: T cells; cancer; galectin-1; immune-suppressive cytokines.

MeSH terms

  • Animals
  • Cells, Cultured
  • Concanavalin A / pharmacology
  • Cytokines* / metabolism
  • Galectin 1* / genetics
  • Galectin 1* / metabolism
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • T-Lymphocytes* / drug effects
  • T-Lymphocytes* / immunology
  • T-Lymphocytes* / metabolism

Substances

  • Galectin 1
  • Cytokines
  • Concanavalin A

Grants and funding

The study was funded by Galecto Biotech.