Galectin-3 is a 31 kD lectin that modulates T cell responses through several mechanisms including apoptosis, TCR cross linking, and TCR down regulation. We found patients with pancreatic ductal adenocarcinoma (PDA) responding to a granulocyte-macrophage colony-stimulating factor (GM-CSF) secreting allogeneic PDA vaccine developed post immunization neutralizing antibodies to galectin-3. We show that galectin-3 binds activated antigen-committed CD8+ T cells only in the tumor microenvironment (TME). 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 (pDCs), which are superior to conventional dendritic cells (cDCs) in activating CD8+ T cells. Thus, inhibiting galectin-3 in conjunction with CD8+ T cell directed immunotherapies should enhance the tumor specific immune response.
- Received August 14, 2014.
- Revision received January 23, 2015.
- Accepted February 8, 2015.
- Copyright © 2015, American Association for Cancer Research.