TY - JOUR
T1 - Interferon γ and tumor necrosis factor have a role in tumor regressions mediated by murine CD8+ tumor-infiltrating lymphocytes
AU - Barth, Richard J.
AU - Mulé, James J.
AU - Spiess, Paul J.
AU - Rosenberg, Steven A.
PY - 1991
Y1 - 1991
N2 - We have investigated the mechanisms whereby adoptively transferred marine CD8+ lymphocytes mediate tumor regressions. Noncytolytic, CD8+ tumor-infiltrating lymphocytes (TIL) eradicated established lung tumors in irradiated mice. Many cytolytic and noncytolytic CD8+ TIL cultures specifically secreted interferon γ (IFN-γ) and tumor necrosis factor when stimulated with tumor cells in vitro. The effectiveness of TIL when adoptively transferred to mice bearing micrometastases correlated better with their ability to specifically secrete lymphokines than with their cytotoxicity in vitro. In 14 of 15 tests, therapeutically effective TIL specifically secreted IFN-γ in vitro, whereas only 1 of 11 ineffective TIL specifically secreted IFN-γ. In contrast, only 8 of 15 therapeutically effective TIL were cytolytic. Antibodies to TNF inhibited the effectiveness of two adoptively transferred TIL cultures. In five experiments, antibodies to IFN-γ abrogated the ability of four different CD8+ TIL cultures to mediate tumor regressions, indicating that secretion of IFN-γ is an essential part of the mechanism of action of TIL.
AB - We have investigated the mechanisms whereby adoptively transferred marine CD8+ lymphocytes mediate tumor regressions. Noncytolytic, CD8+ tumor-infiltrating lymphocytes (TIL) eradicated established lung tumors in irradiated mice. Many cytolytic and noncytolytic CD8+ TIL cultures specifically secreted interferon γ (IFN-γ) and tumor necrosis factor when stimulated with tumor cells in vitro. The effectiveness of TIL when adoptively transferred to mice bearing micrometastases correlated better with their ability to specifically secrete lymphokines than with their cytotoxicity in vitro. In 14 of 15 tests, therapeutically effective TIL specifically secreted IFN-γ in vitro, whereas only 1 of 11 ineffective TIL specifically secreted IFN-γ. In contrast, only 8 of 15 therapeutically effective TIL were cytolytic. Antibodies to TNF inhibited the effectiveness of two adoptively transferred TIL cultures. In five experiments, antibodies to IFN-γ abrogated the ability of four different CD8+ TIL cultures to mediate tumor regressions, indicating that secretion of IFN-γ is an essential part of the mechanism of action of TIL.
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M3 - Article
C2 - 1900079
AN - SCOPUS:0025974725
SN - 0022-1007
VL - 173
SP - 647
EP - 658
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 3
ER -