| First Author | Gerbitz A | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 3 | Pages | e34552 |
| PubMed ID | 22479645 | Mgi Jnum | J:187120 |
| Mgi Id | MGI:5435375 | Doi | 10.1371/journal.pone.0034552 |
| Citation | Gerbitz A, et al. (2012) Stromal interferon-gamma signaling and cross-presentation are required to eliminate antigen-loss variants of B cell lymphomas in mice. PLoS One 7(3):e34552 |
| abstractText | 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. |
