title: Effect of human natural killer and gammadelta T cells on the growth of human autologous melanoma xenografts in SCID mice.
abstract: Natural killer (NK) cells were first identified for their ability to kill tumor cells of different origin in vitro. Similarly, gammadelta T lymphocytes display strong cytotoxic activity against various tumor cell lines. However, the ability of both the NK and gammadelta cells to mediate natural immune response against human malignant tumors in vivo is still poorly defined. Severe combined immunodeficient (SCID) mice have been successfully engrafted with human tumors. In this study, the antitumor effect of local as well as of systemic treatments based on NK cells or Vdelta1 or Vdelta2 gamma/delta T lymphocytes against autologous melanoma cells was investigated in vivo. The results show that all three of the populations were effective in preventing growth of autologous human melanomas when both tumor and lymphoid cells were s.c. inoculated at the same site. However, when lymphoid cells were infused i.v., only NK cells and Vdelta1 gamma/delta T lymphocytes could either prevent or inhibit the s.c. growth of autologous melanoma. Accordingly, both NK cells and Vdelta1 gammadelta T lymphocytes could be detected at the s.c. tumor site. In contrast, Vdelta2 gammadelta T lymphocytes were only detectable in the spleen of the SCID mice. Moreover, NK cells maintained their inhibitory effect on tumor growth even after discontinuation of the treatment. Indeed they were present at the tumor site for a longer period. These data support the possibility to exploit NK cells and Vdelta1 gammadelta T lymphocytes in tumor immunotherapy. Moreover, our study emphasizes the usefulness of human tumor/SCID mouse models for preclinical evaluation of immunotherapy protocols against human tumors.
authors.affiliation: Laboratories of Immunology and Virology, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Lozupone
authors.forename: Daniela
authors.initials: D
authors.lastname: Pende
authors.forename: Vito Lelio
authors.initials: VL
authors.lastname: Burgio
authors.forename: Chiara
authors.initials: C
authors.lastname: Castelli
authors.forename: Massimo
authors.initials: M
authors.lastname: Spada
authors.forename: Massimo
authors.initials: M
authors.lastname: Venditti
authors.forename: Francesca
authors.initials: F
authors.lastname: Luciani
authors.forename: Luana
authors.initials: L
authors.lastname: Lugini
authors.forename: Cristina
authors.initials: C
authors.lastname: Federici
authors.forename: Carlo
authors.initials: C
authors.lastname: Ramoni
authors.forename: Licia
authors.initials: L
authors.lastname: Rivoltini
authors.forename: Giorgio
authors.initials: G
authors.lastname: Parmiani
authors.forename: Filippo
authors.initials: F
authors.lastname: Belardelli
authors.forename: Paola
authors.initials: P
authors.lastname: Rivera
authors.forename: Stefania
authors.initials: S
authors.lastname: Marcenaro
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moretta
authors.forename: Stefano
authors.initials: S
authors.lastname: Fais
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis / Q000235:genetics; D002455:Cell Division; D004247:DNA / Q000032:analysis / Q000235:genetics; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008545:Melanoma / Q000276:immunology*; D051379:Mice; D016513:Mice, SCID; D016133:Polymerase Chain Reaction; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014183:Transplantation, Heterologous / Q000379:methods
chemical_list: D015703:Antigens, CD; D016692:Receptors, Antigen, T-Cell, gamma-delta; D004247:DNA