Abstract
Lymphokine-activated killer (LAK) cells are cytotoxic for a variety of autologous and allogeneic tumor cells as well as modified autologous cells. It is assumed that LAK cells lyse their targets solely by direct cell to cell contact, possibly involving the degranulation and exocytosis of pore-forming elements, similar to that observed with cytotoxic T lymphocytes and NK cells. Reported here are studies demonstrating that LAK cells release factor(s) that are cytotoxic for a human breast carcinoma cell line, MCF-7, when stimulated with tumor cells. The factor(s) are slow acting and maximum cytotoxicity is observed only in a 72-h cytotoxic assay. The ability of LAK cells to secrete cytotoxic factor(s) is dependent on both the ratio of LAK cells to stimulating tumor cells as well as the length of their coincubation. A number of similarly slow acting cytokines that are cytostatic and/or cytotoxic for tumor cells have been described. We tested the ability of specific polyclonal antibodies directed against TNF, IFN-α, IFN-β, and IFN-γ to neutralize the cytotoxic supernatant activity. Only antibodies specific for IFN-γ and TNF were neutralizing. We measured the amounts of IFN-γ and TNF in the cytotoxic supernatants and determined that increased amounts of IFN-γ and TNF were released after LAK cell-tumor cell interactions compared to supernatants of LAK cells alone or tumor cell alone. Comparable concentrations of human rIFN-γ and rTNF resulted in similar levels (50 to 90%) of MCF-7 cell cytotoxicity as those observed with the stimulated LAK cell supernatants. We thus concluded that the majority of the cytotoxic activity released by LAK cells when stimulated with tumor cells was attributed to the synergistic activities of IFN-γ and TNF. The significance of these observations in relation to the possible mechanisms by whick LAK cells mediate cytolysis is discussed.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2133-2139 |
| Number of pages | 7 |
| Journal | Journal of Immunology |
| Volume | 142 |
| Issue number | 6 |
| State | Published - 1989 |
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ASJC Scopus subject areas
- Immunology
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Tumor targets stimulate IL-2 activated killer cells to produce interferon-γ and tumor necrosis factor. / Chong, A. S F; Scuderi, P.; Grimes, W. J.; Hersh, Evan M.
In: Journal of Immunology, Vol. 142, No. 6, 1989, p. 2133-2139.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Tumor targets stimulate IL-2 activated killer cells to produce interferon-γ and tumor necrosis factor
AU - Chong, A. S F
AU - Scuderi, P.
AU - Grimes, W. J.
AU - Hersh, Evan M
PY - 1989
Y1 - 1989
N2 - Lymphokine-activated killer (LAK) cells are cytotoxic for a variety of autologous and allogeneic tumor cells as well as modified autologous cells. It is assumed that LAK cells lyse their targets solely by direct cell to cell contact, possibly involving the degranulation and exocytosis of pore-forming elements, similar to that observed with cytotoxic T lymphocytes and NK cells. Reported here are studies demonstrating that LAK cells release factor(s) that are cytotoxic for a human breast carcinoma cell line, MCF-7, when stimulated with tumor cells. The factor(s) are slow acting and maximum cytotoxicity is observed only in a 72-h cytotoxic assay. The ability of LAK cells to secrete cytotoxic factor(s) is dependent on both the ratio of LAK cells to stimulating tumor cells as well as the length of their coincubation. A number of similarly slow acting cytokines that are cytostatic and/or cytotoxic for tumor cells have been described. We tested the ability of specific polyclonal antibodies directed against TNF, IFN-α, IFN-β, and IFN-γ to neutralize the cytotoxic supernatant activity. Only antibodies specific for IFN-γ and TNF were neutralizing. We measured the amounts of IFN-γ and TNF in the cytotoxic supernatants and determined that increased amounts of IFN-γ and TNF were released after LAK cell-tumor cell interactions compared to supernatants of LAK cells alone or tumor cell alone. Comparable concentrations of human rIFN-γ and rTNF resulted in similar levels (50 to 90%) of MCF-7 cell cytotoxicity as those observed with the stimulated LAK cell supernatants. We thus concluded that the majority of the cytotoxic activity released by LAK cells when stimulated with tumor cells was attributed to the synergistic activities of IFN-γ and TNF. The significance of these observations in relation to the possible mechanisms by whick LAK cells mediate cytolysis is discussed.
AB - Lymphokine-activated killer (LAK) cells are cytotoxic for a variety of autologous and allogeneic tumor cells as well as modified autologous cells. It is assumed that LAK cells lyse their targets solely by direct cell to cell contact, possibly involving the degranulation and exocytosis of pore-forming elements, similar to that observed with cytotoxic T lymphocytes and NK cells. Reported here are studies demonstrating that LAK cells release factor(s) that are cytotoxic for a human breast carcinoma cell line, MCF-7, when stimulated with tumor cells. The factor(s) are slow acting and maximum cytotoxicity is observed only in a 72-h cytotoxic assay. The ability of LAK cells to secrete cytotoxic factor(s) is dependent on both the ratio of LAK cells to stimulating tumor cells as well as the length of their coincubation. A number of similarly slow acting cytokines that are cytostatic and/or cytotoxic for tumor cells have been described. We tested the ability of specific polyclonal antibodies directed against TNF, IFN-α, IFN-β, and IFN-γ to neutralize the cytotoxic supernatant activity. Only antibodies specific for IFN-γ and TNF were neutralizing. We measured the amounts of IFN-γ and TNF in the cytotoxic supernatants and determined that increased amounts of IFN-γ and TNF were released after LAK cell-tumor cell interactions compared to supernatants of LAK cells alone or tumor cell alone. Comparable concentrations of human rIFN-γ and rTNF resulted in similar levels (50 to 90%) of MCF-7 cell cytotoxicity as those observed with the stimulated LAK cell supernatants. We thus concluded that the majority of the cytotoxic activity released by LAK cells when stimulated with tumor cells was attributed to the synergistic activities of IFN-γ and TNF. The significance of these observations in relation to the possible mechanisms by whick LAK cells mediate cytolysis is discussed.
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UR - http://www.scopus.com/inward/citedby.url?scp=0024603477&partnerID=8YFLogxK
M3 - Article
C2 - 2493506
AN - SCOPUS:0024603477
VL - 142
SP - 2133
EP - 2139
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 6
ER -