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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., Sukumar, M., Helm, F., Wilke, A., Friese, C., Fahrenwaldt, C., Lehmann, F.M., Loddenkemper, C., Kammertoens, T., Mautner, J., Schmitt, C.A., 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 |
| ISSN: | 1932-6203 |
| Publisher: | Public Library of Science |
| Volume: | 7 |
| Number: | 3 |
| 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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