par Demotte, Nathalie;Wieërs, Grégoire;Van Der Smissen, Patrick;Moser, Muriel ;Schmidt, Christopher;Thielemans, Kris M.;Squifflet, Jean-Luc;Weynand, Birgit;Carrasco, Javier;Lurquin, Christophe;Courtoy, Pierre ;van der Bruggen, Pierre
Référence Cancer research, 70, 19, page (7476-7488)
Publication Publié, 2010-10
Référence Cancer research, 70, 19, page (7476-7488)
Publication Publié, 2010-10
Article révisé par les pairs
Résumé : | Human CD8(+) tumor-infiltrating T lymphocytes (TIL), in contrast with CD8(+) blood cells, show impaired IFN-γ secretion on ex vivo restimulation. We have attributed the impaired IFN-γ 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-γ 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-γ 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. |