1. Activated iNKT cells promote Vγ9Vδ2-T cell anti-tumor effector functions through the production of TNF-α
- Author
-
Schneiders, Famke L., de Bruin, Renée C.G., Santegoets, Saskia J.A.M., Bonneville, Marc, Scotet, Emmanuel, Scheper, Rik J., Verheul, Henk M.W., de Gruijl, Tanja D., and van der Vliet, Hans J.
- Subjects
- *
PROMOTERS (Genetics) , *TUMOR necrosis factors , *LYMPHOCYTES , *T cells , *ANTINEOPLASTIC agents , *DENDRITIC cells , *IMMUNE response - Abstract
Abstract: Vγ9Vδ2-T cells constitute a proinflammatory lymphocyte subpopulation with established antitumor activity. Phosphoantigens activate Vγ9Vδ2-T cells in vivo and in vitro. We studied whether the antitumor activity of Vγ9Vδ2-T cells can be potentiated by invariant NKT cells (iNKT), an important immunoregulatory T cell subset. When activated by the glycolipid α-galactosylceramide (α-GalCer), iNKT produce large amounts of cytokines involved in antitumor immune responses. Monocyte-derived dendritic cells were loaded with both phosphoantigens (using aminobisphosphonates) and α-GalCer during maturation and subsequently co-cultured with Vγ9Vδ2-T and iNKT cells. Aminobisphosphonates dose-dependently enhanced Vγ9Vδ2-T cell activation, and this was potentiated by α-GalCer-induced iNKT co-activation. iNKT co-activation also enhanced the IFN-γ production and cytolytic potential of Vγ9Vδ2-T cells against tumor cells. Using transwell experiments and neutralizing antibodies cross-talk between iNKT and Vγ9Vδ2-T cells was found to be mediated by TNF-α. Our data provide a rationale for combining both activating ligands to improve Vγ9Vδ2-T cell based approaches in cancer-immunotherapy. [Copyright &y& Elsevier]
- Published
- 2012
- Full Text
- View/download PDF