Inhibition of caspases maintains the antineoplastic function of gammadelta T cells repeatedly challenged with lymphoma cells.
T lymphocytes recognizing tumor antigens eventually undergo anergy or Fas-mediated death. V gamma9/V delta2+ T cells recognize poorly characterized ligand moieties on human B-cell lymphomas. Here we show that gammadelta 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 gammadelta T cell survival and sustained the killing of neoplastic cells and the release of IFN-gamma and tumor necrosis factor alpha. Caspases of tumor-specific T cells represent a candidate target to complement adoptive immunotherapy strategies.
Ferrarini
M
M
Department of Medicine, Hospital San Raffaele Scientific Institute, Milano, Italy. m.ferrarini@hsr.it
Consogno
G
G
Rovere
P
P
Sciorati
C
C
Dagna
L
L
Resta
D
D
Rugarli
C
C
Manfredi
A A
AA
D000951:Antigens, Neoplasm / Q000276:immunology; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D061945:Caspase Inhibitors; D020169:Caspases / Q000276:immunology; D002450:Cell Communication; D004789:Enzyme Activation; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008223:Lymphoma / Q000276:immunology* / Q000473:pathology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000951:Antigens, Neoplasm; D061945:Caspase Inhibitors; D016692:Receptors, Antigen, T-Cell, gamma-delta; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases