Diverse effect of cytokine treatment of tumor cells on specific versus non-specific cytotoxicity.
The effect of IFN-gamma and TNF-alpha treatment of an ovarian carcinoma line on the sensitivity to lysis by specific CTL clones and non-specific Tumor Associated Lymphocytes (TAL), isolated from the ascites fluid, was analyzed. The in vitro established TAL line displayed a non-specific lytic activity against the autologous tumor as well as against several allogeneic tumor lines. Pretreatment with IFN-gamma alone, or in combination with TNF-alpha, rendered the carcinoma line less susceptible to lysis by the autologous TAL line. Conversely, susceptibility to lysis by tumor specific T cell clones, isolated from the TAL line, was increased as a result of cytokine pretreatment. Several TCR-alpha/beta+, CD8+ T-cell clones showing a more specific pattern of lysis against the autologous tumor were isolated. Lysis of the autologous tumor by these clones involved the TCR-alpha/beta via a MHC-class I restricted mechanism dependent on the adhesion molecules ICAM-1 and LFA-3, as inferred from antibody blocking studies. The enhanced sensitivity to specific CTL clones seen after cytokine treatment may be related to the enhanced expression of ICAM-1 molecules on the ovarian carcinoma. These results have implications for cytokine based immunotherapy, where IFN-gamma may enhance the effects of tumor associated specific CTL while decreasing that of non-specific effector cells.
Naganuma
H
H
Department of Immunology, Karolinska Institute, Stockholm, Sweden.
Halapi
E
E
Masucci
G
G
Hansson
M
M
Wersäll
P
P
Hising
C
C
Venkateswaran
S
S
Mellstedt
H
H
Kiessling
R
R
D001202:Ascitic Fluid / Q000276:immunology; D002999:Clone Cells; D016207:Cytokines / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000008:administration & dosage / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000628:therapy*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000494:pharmacology*
D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma