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Titolo:
Immunopotentiating role of IFN-gamma in early and late stages of type 1 CD8 effector cell-mediated tumor rejection
Autore:
Dobrzanski, MJ; Reome, JB; Dutton, RW;
Indirizzi:
Trudeau Inst Inc, Saranac Lake, NY 12983 USA Trudeau Inst Inc Saranac Lake NY USA 12983 nc, Saranac Lake, NY 12983 USA
Titolo Testata:
CLINICAL IMMUNOLOGY
fascicolo: 1, volume: 98, anno: 2001,
pagine: 70 - 84
SICI:
1521-6616(200101)98:1<70:IROIIE>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
RECOMBINANT INTERFERON-GAMMA; T-CELLS; IN-VIVO; MELANOMA-CELLS; INFILTRATING LYMPHOCYTES; METASTATIC MELANOMA; NECROSIS-FACTOR; CANCER; ALPHA; CARCINOMA;
Keywords:
immunotherapy; melanoma; metastases; chemokines; tumor immunity;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
45
Recensione:
Indirizzi per estratti:
Indirizzo: Dobrzanski, MJ Trudeau Inst Inc, POB 59, Saranac Lake, NY 12983 USA Trudeau Inst Inc POB 59 Saranac Lake NY USA 12983 12983 USA
Citazione:
M.J. Dobrzanski et al., "Immunopotentiating role of IFN-gamma in early and late stages of type 1 CD8 effector cell-mediated tumor rejection", CLIN IMMUNO, 98(1), 2001, pp. 70-84

Abstract

Type 1 cytolytic CD8 effector T cells (Tc1) characteristically secrete IFN-gamma. Using an OVA-transfected B16 melanoma lung tumor model, we show that OVA Ag-specific Tc1 cells mediate a reduction in tumor growth that significantly prolongs survival in tumor-bearing mice. Transfer of Tc1 cells fromOT-I mice crossed to IFN-gamma -KO mice showed that IFN-gamma -deficient Tc1 effector cells were less therapeutically effective than corresponding cells from wildtype mice. Therapeutic effects were dependent, in part, on effector cell-derived IFN-gamma, which not only induced elevated levels of lung-derived IP-10 and RANTES chemokine message in vivo, but also increased the local accumulation of activated host-derived CD4(+)/CD44(High), CD8(+)/CD44(High), and non-T-immune cell populations at the tumor site. Over time, the numbers of host-derived immune cells increased in the lung, which correlated with an elevated production of IP-10 and RANTES and a continued reduction in tumor burden. Conversely, donor Tc1 cell numbers markedly diminishedat corresponding times, suggesting that prolonged therapeutic responses were due to the presence of host-derived antitumor mechanisms. Moreover, adoptive transfer of IFN-gamma -deficient Tc1 cells into tumor-bearing IFN-gamma -KO recipients showed that both recipient and donor-derived IFN-gamma play a significant role in Tc1-mediated responses and that Tc1 effector cell immunotherapy is predominantly mediated by IFN-gamma -dependent mechanisms. (C) 2000 Academic Press.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/04/20 alle ore 19:36:24