Data from Galectin-3 Shapes Antitumor Immune Responses by Suppressing CD8+ T Cells via LAG-3 and Inhibiting Expansion of Plasmacytoid Dendritic Cells
Year: 2023
Type: other
Abstract: Galectin-3 is a 31-kDa lectin that modulates T-cell responses through several mechanisms, including apoptosis, T-cell receptor (TCR) cross-linking, and TCR downregulation. We found that patients with pancreatic ductal adenocarcinoma (PDA) who responded to a granulocyte-macrophage colony-stimulating factor–secreting allogeneic PDA vaccine developed neutralizing antibodies to galectin-3 after immunization. We show that galectin-3 binds activated antigen-committed CD8+ T cells only in the tumor microenvironment. Galectin-3–deficient mice exhibit improved CD8+ T-cell effector function and increased expression of several inflammatory genes. Galectin-3 binds to LAG-3, and LAG-3 expression is necessary for galectin-3–mediated suppression of CD8+ T cells in vitro. Lastly, galectin-3–deficient mice have elevated levels of circulating plasmacytoid dendritic cells, which are superior to conventional dendritic cells in activating CD8+ T cells. Thus, inhibiting galectin-3 in conjunction with CD8+ T-cell–directed immunotherapies should enhance the tumor-specific immune response. Cancer Immunol Res; 3(4); 412–23. ©2015 AACR.
Authors: Theodore Kouo, Lanqing Huang, Alexandra B. Pucsek, Minwei Cao, Sara Solt, Todd Armstrong, Elizabeth Jaffee
Language: English
Topic: Galectins and Cancer Biology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W4362546130