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 Citations (Scopus)

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

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Interferons
Monoclonal Antibodies
T-Lymphocytes
Neoplasms
Therapeutics
Therapeutic Uses
Neutralizing Antibodies
Lymph Nodes
Antigens
Growth

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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

In: Cancer Research, Vol. 62, No. 15, 01.08.2002, p. 4413-4418.

Research output: Contribution to journalArticle

Wilcox, Ryan A. ; Flies, Dallas B. ; Wang, Hao ; Tamada, Koji ; Johnson, Aaron J. ; Pease, Larry R ; Rodriguez, Moses ; Guo, Yajun ; Chen, Lieping. / 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. In: Cancer Research. 2002 ; Vol. 62, No. 15. pp. 4413-4418.
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