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Robust Ability of IFN-γ to Upregulate Class II MHC Antigen Expression in Tumor Bearing Rat Brains

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Abstract

T cells are attractive for delivering therapy to brain tumor, especially disseminated micro-tumor. However, to trigger effector function, tumor antigen must be re-presented to T cells, via major histocompatibility complex (MHC) proteins, at the tumor site. In normal brain, MHC+ antigen-presenting cells (APC) are rare, but abundant after gamma interferon (IFN-γ) injection. Here we studied tumor-bearing brains. IFN-γ (or buffer) was injected stereotactically into brains with established tumors from a panel of immunologically varied glioma cell lines, some expressing b-galactosidase as a micro-tumor marker. Four days later, cryostat sections were stained for tumor and MHC proteins. In phosphate-buffered saline-injected controls, class II MHC+ potential APC (microglia, macrophages) were seen only at (some) tumor sites. In rats that received IFN-γ, class II+ potential APC were widespread, including all actual and potential micro-tumor sites and all tumor-free areas. In the same slides, neither class I nor class II MHC antigen was detected in neural cells or most tumor cells. This MHC pattern favors indirect re-presentation of tumor antigen, by tumor-adjacent APC. The robust response to IFN-γ might also be exploited in other ways: activated microglia and macrophages can attack tumor directly, and class II+ APC may help mark micro-tumor sites.

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Authors and Affiliations

  1. Brain Tumor Immunology Laboratory, Department of Neurosurgery, Brigham and Women's Hospital and Harvard Medical School, CNS &, Boston, MA

    Tanya Dutta & Lois A. Lampson

  2. Department of Neurology, University of Washington, Seattle, WA, USA

    Alexander Spence

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  1. Tanya Dutta
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  2. Alexander Spence
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  3. Lois A. Lampson
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Dutta, T., Spence, A. & Lampson, L.A. Robust Ability of IFN-γ to Upregulate Class II MHC Antigen Expression in Tumor Bearing Rat Brains. J Neurooncol 64, 31–44 (2003). https://doi.org/10.1023/A:1024973506989

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