Cancer dormancy. VII. A regulatory role for CD8+ T cells and IFN-γ in establishing and maintaining the tumor-dormant state

J. David Farrar, Kathy H. Katz, Jana Windsor, Gerald Thrush, Richard H. Scheuermann, Jonathan W. Uhr, Nancy E. Street

Research output: Contribution to journalArticle

104 Scopus citations

Abstract

Dormant tumor cells resistant to ablative cancer therapy represent a significant clinical obstacle due to later relapse. Experimentally, the murine B cell lymphoma (BCL1) is used as a model of tumor dormancy in mice vaccinated with the BCL1 Ig. Here, we used this model to explore the cellular mechanisms underlying dormancy. Our previous studies have demonstrated that T cell-mediated immunity is an important component in the regulation of tumor dormancy because Id-immune T cells adoptively transferred into passively immunized SCID mice challenged with BCL1 cells significantly increased the incidence and duration of the dormant state. We have extended these observations and demonstrate that CD8+, but not CD4+, T cells are required for the maintenance of dormancy in BCL1 Ig-immunized BALB/c mice. In parallel studies, the transfer of Id-immune CD8+ cells, but not Id- immune CD4+ cells, conferred significant protection to SCID mice passively immunized with nonprotective levels of polyclonal anti-Id and then challenged with BCL1 cells. Furthermore, the ability of CD8+ T cells to induce a state of dormancy in passively immunized SCID mice was completely abrogated by treatment with neutralizing α-IFN-γ mAbs in vivo. In vitro studies demonstrated that IFN-γ alone or in combination with reagents to cross-link the surface Ig induced both cell cycle arrest and apoptosis in a BCL1 cell line. Collectively, these data demonstrate a role for CD8+ T cells via endogenous production of IFN-γ in collaboration with humoral immunity to both induce and maintain a state of tumor dormancy.

Original languageEnglish (US)
Pages (from-to)2842-2849
Number of pages8
JournalJournal of Immunology
Volume162
Issue number5
StatePublished - Mar 1 1999

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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