Cytokine production by T-cell lines derived from tumor-infiltrating lymphocytes from patients with ovarian carcinoma: tumor-specific immune responses and inhibition of antigen-independent cytokine production by ovarian tumor cells.
The ability of T-cell lines derived from tumor-infiltrating lymphocytes (TIL) from patients with ovarian carcinoma to produce interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and IL-6 in response to autologous or allogeneic ovarian carcinoma tumor cells was determined. These T-cell lines were derived in low concentrations of recombinant IL-2 (rIL-2), 200 IU/ml. Certain of these T-cell lines (3 of 7) exhibited antigen-independent (spontaneous) production of moderate to low concentrations of IFN-gamma (75 to 112 pg/ml), TNF-alpha (62-88 pg/ml), and IL-6 (38 to 690 pg/ml), in culture medium alone in the absence of rIL-2, tumor cells or polyclonal activators. Addition of 20 IU/ml of rIL-2 to the cultures resulted in a significant increase of the antigen-independent production of IFN-gamma (range 75-6480 pg/ml) by all seven T-cell lines and TNF-alpha (44-490 pg/ml) by 5 of 7 T-cell lines. Certain T-cell lines (4 of 7) exhibited antigen-independent production of IL-6 (38-690 pg/ml), which was not affected by the addition of 20 IU/ml of rIL-2. Certain TIL-derived T-cell lines (2 of 7) produced IFN-gamma, TNF-alpha, and IL-6 in response to stimulation with autologous ovarian tumor cells, in the presence of 20 IU/ml of rIL-2. Irradiated autologous ovarian tumor cells alone or in the presence of rIL-2 did not produce any detectable levels of IFN-gamma, TNF-alpha, or IL-6 during the 6 day culture.(ABSTRACT TRUNCATED AT 250 WORDS)
Kooi
S
S
Department of Immunology, University of Texas, M.D. Anderson Cancer Center, Houston 77030.
Freedman
R S
RS
Rodriguez-Villanueva
J
J
Platsoucas
C D
CD
D015703:Antigens, CD / Q000032:analysis; D016516:CD4-CD8 Ratio; D002460:Cell Line; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis*; D003602:Cytotoxicity, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D015703:Antigens, CD; D016207:Cytokines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma