Journal
CANCER RESEARCH
Volume 70, Issue 19, Pages 7476-7488Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-10-0761
Keywords
-
Categories
Funding
- Fondation contre le Cancer (Belgium), Fonds de la Recherche Scientifique Medicale (Belgium)
- European Community [518234]
- Fonds National de la Recherche Scientifique (Belgium)
- FNRS
- Region Bruxelloise
- Region Wallonne
- Loterie Nationale
- Interuniversity Attraction Poles
- Universite Catholique de Louvain (Belgium)
Ask authors/readers for more resources
Human CD8(+) tumor-infiltrating T lymphocytes (TIL), in contrast with CD8(+) blood cells, show impaired IFN-gamma secretion on ex vivo restimulation. We have attributed the impaired IFN-gamma secretion to a decreased mobility of T-cell receptors on trapping in a lattice of glycoproteins clustered by extracellular galectin-3. Indeed, we have previously shown that treatment with N-acetyllactosamine, a galectin ligand, restored this secretion. We strengthened this hypothesis here by showing that CD8+ TIL treated with an anti-galectin-3 antibody had an increased IFN-gamma secretion. Moreover, we found that GCS-100, a polysaccharide in clinical development, detached galectin-3 from TIL and boosted cytotoxicity and secretion of different cytokines. Importantly, we observed that not only CD8(+) TIL but also CD4(+) TIL treated with GCS-100 secreted more IFN-gamma on ex vivo restimulation. In tumor-bearing mice vaccinated with a tumor antigen, injections of GCS-100 led to tumor rejection in half of the mice, whereas all control mice died. In nonvaccinated mice, GCS-100 had no effect by itself. These results suggest that a combination of galectin-3 ligands and therapeutic vaccination may induce more tumor regressions in cancer patients than vaccination alone. Cancer Res; 70(19); 7476-88. (C) 2010 AACR.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available