Interferon γ and tumor necrosis factor have a role in tumor regressions mediated by murine CD8+ tumor-infiltrating lymphocytes

Richard J. Barth, James J. Mulé, Paul J. Spiess, Steven A. Rosenberg

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)647-658
Number of pages12
JournalJournal of Experimental Medicine
Volume173
Issue number3
StatePublished - 1991
Externally publishedYes

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Tumor-Infiltrating Lymphocytes
Interferons
Tumor Necrosis Factor-alpha
Neoplasms
Neoplasm Micrometastasis
Antibodies
Lymphokines
Lymphocytes
Lung

ASJC Scopus subject areas

  • Immunology

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Interferon γ and tumor necrosis factor have a role in tumor regressions mediated by murine CD8+ tumor-infiltrating lymphocytes. / Barth, Richard J.; Mulé, James J.; Spiess, Paul J.; Rosenberg, Steven A.

In: Journal of Experimental Medicine, Vol. 173, No. 3, 1991, p. 647-658.

Research output: Contribution to journalArticle

Barth, Richard J. ; Mulé, James J. ; Spiess, Paul J. ; Rosenberg, Steven A. / Interferon γ and tumor necrosis factor have a role in tumor regressions mediated by murine CD8+ tumor-infiltrating lymphocytes. In: Journal of Experimental Medicine. 1991 ; Vol. 173, No. 3. pp. 647-658.
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