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Stromal interferon-γ signaling and cross-presentation are required to eliminate antigen-loss variants of B cell lymphomas in mice

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Item Type:Article
Title:Stromal interferon-γ signaling and cross-presentation are required to eliminate antigen-loss variants of B cell lymphomas in mice
Creators Name:Gerbitz, A. and Sukumar, M. and Helm, F. and Wilke, A. and Friese, C. and Fahrenwaldt, C. and Lehmann, F.M. and Loddenkemper, C. and Kammertoens, T. and Mautner, J. and Schmitt, C.A. and Blankenstein, T. and Bornkamm, G.W.
Abstract:To study mechanisms of T cell-mediated rejection of B cell lymphomas, we developed a murine lymphoma model wherein three potential rejection antigens, human c-MYC, chicken ovalbumin (OVA), and GFP are expressed. After transfer into wild-type mice 60-70% of systemically growing lymphomas expressing all three antigens were rejected; lymphomas expressing only human c-MYC protein were not rejected. OVA expressing lymphomas were infiltrated by T cells, showed MHC class I and II upregulation, and lost antigen expression, indicating immune escape. In contrast to wild-type recipients, 80-100% of STAT1-, IFN-{gamma}-, or IFN-{gamma} receptor-deficient recipients died of lymphoma, indicating that host IFN-{gamma} signaling is critical for rejection. Lymphomas arising in IFN-{gamma}- and IFN-{gamma}-receptor-deficient mice had invariably lost antigen expression, suggesting that poor overall survival of these recipients was due to inefficient elimination of antigen-negative lymphoma variants. Antigen-dependent eradication of lymphoma cells in wild-type animals was dependent on cross-presentation of antigen by cells of the tumor stroma. These findings provide first evidence for an important role of the tumor stroma in T cell-mediated control of hematologic neoplasias and highlight the importance of incorporating stroma-targeting strategies into future immunotherapeutic approaches.
Keywords:Antigens, B-Lymphocytes, Green Fluorescent Proteins, Inbred C57BL Mice, Interferon-gamma, Lymphoma, B-Cell, Neoplastic Gene Expression Regulation, Ovalbumin, Proto-Oncogene Proteins c-myc, Signal Transduction, Animals, Chickens, Mice
Source:PLoS ONE
Publisher:Public Library of Science
Page Range:e34552
Date:30 March 2012
Official Publication:https://doi.org/10.1371/journal.pone.0034552
PubMed:View item in PubMed

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