Inhibition of caspases maintains the antineoplastic function of γδ T cells repeatedly challenged with lymphoma cells

T lymphocytes recognizing tumor antigens eventually undergo anergy or Fas-mediated death. Vγ9/Vδ2⁺ T cells recognize poorly characterized ligand moieties on human B-cell lymphomas. Here we show that γδ T cells, a model for the study of activation-induced apoptosis, activate on repeated in vitro antigen-recognition caspase 3 and 8 and dramatically down-regulate their cytotoxic and secretory function. Caspase hindrance enhanced γδ T cell survival and sustained the killing of neoplastic cells and the release of IFN-γ and tumor necrosis factor α. Caspases of tumor-specific T cells represent a candidate target to complement adoptive immunotherapy strategies.