| First Author | Ney JT | Year | 2009 |
| Journal | Hepatology | Volume | 49 |
| Issue | 2 | Pages | 471-81 |
| PubMed ID | 19105207 | Mgi Jnum | J:186226 |
| Mgi Id | MGI:5431209 | Doi | 10.1002/hep.22652 |
| Citation | Ney JT, et al. (2009) Autochthonous liver tumors induce systemic T cell tolerance associated with T cell receptor down-modulation. Hepatology 49(2):471-81 |
| abstractText | The reason the adaptive immune system fails in advanced liver tumors is largely unclear. To address this question, we have developed a novel murine model that combines c-myc-induced autochthonous tumorigenesis with expression of a cognate antigen, ovalbumin (OVA). When c-myc/OVA transgenic mice were crossed with liver-specific inducer mice, multifocal hepatocellular carcinomas co-expressing OVA developed in a tetracycline-dependent manner with a short latency and 100% penetrance. Transferred OVA-specific T cells, although infiltrating the tumor at high numbers, were hyporesponsive, as evidenced by a lack of in vivo cytotoxicity and interferon gamma production. This allowed the tumor to progress even in the presence of large numbers of antigen-specific T cells and even after vaccination (OVA+CpG-DNA). Interestingly, T cell receptor down-modulation was observed, which may explain antigen-specific hyporesponsiveness. This model is helpful in understanding liver cancer-specific mechanisms of T cell tolerance and dissection of antigen-specific and nonspecific mechanisms of immunotherapies in the preclinical phase. |
