Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 107, Issue 10, Pages 4716-4721Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0911587107
Keywords
anti-tumor immunity; brain tumors; immunotherapy
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Funding
- NIH/NINDS [1R01NS44556.01, NS445561.01, 1R21NSO54143.01, 1UO1N-S052465.01, 1RO3TW006273-01, 1RO1NS 057711, 1RO1NS 054193.1, RO1 NS42893.01, U54 NS045309-01, 1R21NS047298-01]
- Medallions Group Endowed Chairs in Gene Therapeutics
- Linda Tallen & David Paul Kane Foundation
- Board of Governors at Cedars-Sinai Medical Center
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To analyze the in vivo structure of antigen-specific immunological synapses during an effective immune response, we established brain tumors expressing the surrogate tumor antigen ovalbumin and labeled antigen-specific anti-glioma T cells using specific tetramers. Using these techniques, we determined that a significant number of antigen-specific T cells were localized to the brain tumor and surrounding brain tissue and a large percentage could be induced to express IFN gamma when exposed to the specific ovalbumin-derived peptide epitope SIINFEKL. Detailed morphological analysis of T cells immunoreactive for tetramers in direct physical contact with tumor cells expressing ovalbumin indicated that the interface between T cells and target tumor cells displayed various morphologies, including Kupfer-type immunological synapses. Quantitative analysis of adjacent confocal optical sections was performed to determine if the higher frequency of antigen-specific anti-glioma T cells present in animals that developed an effective antitumor immune response could be correlated with a specific immunological synaptic morphology. Detailed in vivo quantitative analysis failed to detect an increased proportion of immunological synapses displaying the characteristic Kupfer-type morphology in animals mounting a strong and effective antitumor immune response as compared with those experiencing a clinically ineffective response. We conclude that an effective cytolytic immune response is not dependent on an increased frequency of Kupfer-type immunological synapses between T cells and tumor cells.
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