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Gerbitz, A.* ; Sukumar, M. ; Helm, F.* ; Wilke, A.* ; Friese, C.* ; Fahrenwaldt, C.* ; Lehmann, F.M. ; Loddenkemper, C.* ; Kammertoens, T.* ; Mautner, J. ; Schmitt, C.A.* ; Blankenstein, T.* ; Bornkamm, G.W.

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

PLoS ONE 7:e34552 (2012)
Publ. Version/Full Text Volltext DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Thymic Epithelial-cells; Non-hodgkin-lymphoma; T-cells; Suppressor-cells; Burkitt-lymphoma; Tumor Stroma; In-vivo; Cancer; Lymphocytes; Immunity
ISSN (print) / ISBN 1932-6203
Journal PLoS ONE
Quellenangaben Volume: 7, Issue: 3, Pages: , Article Number: e34552 Supplement: ,
Publisher Public Library of Science (PLoS)
Publishing Place Lawrence, Kan.
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Clinical Molecular Biology and Tumor Genetics (K.MOLBI)
CCG Pediatric Tumor Immunology (AGV-KPT)