Impaired infiltration of tumor-specific cytolytic T cells in the absence of interferon-γ despite their normal maturation in lymphoid organs during CD137 monoclonal antibody therapy

Ryan A. Wilcox, Dallas B. Flies, Hao Wang, Koji Tamada, Aaron J. Johnson, Larry R. Pease, Moses Rodriguez, Yajun Guo, Lieping Chen

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Engagement of CD137 receptor by agonistic monoclonal antibodies (mAb) stimulates IFN-γ production and eradicates established tumors in syngeneic mouse models. Using IFN-γ-deficient mice or neutralizing mAb, we demonstrate that IFN-γ is an absolute requirement for the antitumor effect of CD137 mAb. Despite progressive tumor growth in IFN-γ-depleted mice, a fully competent CD8+ cytolytic T cell (CTL) response developed in the lymph nodes. In addition, tumor cell sensitivity to IFN-γ was not required because expression of a dominant-negative IFN-γ receptor on the tumor did not affect the therapeutic effect of CD137 mAb. However, in the absence of IFN-γ, the number of tumor-infiltrating CD8+ CTLs was drastically decreased. Our results demonstrate that IFN-γ is a critical factor regulating the infiltration of antigen-specific CTL into the tumor.

Original languageEnglish (US)
Pages (from-to)4413-4418
Number of pages6
JournalCancer research
Volume62
Issue number15
StatePublished - Aug 1 2002

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Impaired infiltration of tumor-specific cytolytic T cells in the absence of interferon-γ despite their normal maturation in lymphoid organs during CD137 monoclonal antibody therapy'. Together they form a unique fingerprint.

Cite this