We have investigated the mechanisms whereby adoptively transferred murine 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 invitro. 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.
ASJC Scopus subject areas
- Immunology and Allergy