IL-12 treatment of endogenously arising murine brain tumors

E. J. Roy, U. Gawlick, B. A. Orr, L. A. Rund, A. G. Webb, D. M. Kranz

Research output: Contribution to journalArticle

Abstract

A number of recent studies have indicated that T cells can be stimulated to attack transplanted brain tumors in rodent models. As IL-12 has been shown to activate cytotoxic T cell responses, we tested the idea that it might stimulate a T cell response against endogenous brain tumors that arise in SV40 large T Ag transgenic mice (SV11). SV11 mice develop tumors of the choroid plexus, a specialization of the ependymal lining of the brain ventricles. They are a particularly relevant model of human disease, because they are immunocompetent but immunologically tolerant of the tumors. SV11 mice were treated with recombinant murine IL-12 for 10 days. Tumors grew more slowly than in control treated mice, and in some cases were reduced in size, as assessed by magnetic resonance imaging before and after treatment. At the end of treatment, tumors, but not brain parenchyma, exhibited extensive infiltration of activated CD8+ and CD4+ T cells. Tumors also showed a reduction in vascular density. Mice treated with IL-12 lived significantly longer than control mice. Tumors that progressed were nearly devoid of T cells, indicating that the T cell response was not sustained. In addition, some mice that had a substantial tumor burden at the beginning of treatment displayed evidence of immunosuppression, which might be related to TGF-β2 detected in tumors. We conclude that IL-12 treatment can initiate an anti-tumor response even against endogenously arising brain tumors, but factors that will allow a sustained and more effective anti-tumor response need to be determined.

Original languageEnglish (US)
Pages (from-to)7293-7299
Number of pages7
JournalJournal of Immunology
Volume165
Issue number12
DOIs
StatePublished - Dec 15 2000

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Interleukin-12
Brain Neoplasms
T-Lymphocytes
Neoplasms
Therapeutics
Choroid Plexus Neoplasms
Tumor Burden
Interleukin-10
Immunosuppression
Transgenic Mice
Blood Vessels
Rodentia
Magnetic Resonance Imaging
Brain

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

IL-12 treatment of endogenously arising murine brain tumors. / Roy, E. J.; Gawlick, U.; Orr, B. A.; Rund, L. A.; Webb, A. G.; Kranz, D. M.

In: Journal of Immunology, Vol. 165, No. 12, 15.12.2000, p. 7293-7299.

Research output: Contribution to journalArticle

Roy, E. J. ; Gawlick, U. ; Orr, B. A. ; Rund, L. A. ; Webb, A. G. ; Kranz, D. M. / IL-12 treatment of endogenously arising murine brain tumors. In: Journal of Immunology. 2000 ; Vol. 165, No. 12. pp. 7293-7299.
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