| First Author | Johansson A | Year | 2012 |
| Journal | Proc Natl Acad Sci U S A | Volume | 109 |
| Issue | 20 | Pages | 7841-6 |
| PubMed ID | 22547817 | Mgi Jnum | J:318835 |
| Mgi Id | MGI:6861947 | Doi | 10.1073/pnas.1118296109 |
| Citation | Johansson A, et al. (2012) Tumor-targeted TNFalpha stabilizes tumor vessels and enhances active immunotherapy. Proc Natl Acad Sci U S A 109(20):7841-6 |
| abstractText | Solid tumors are intrinsically resistant to immune rejection. Abnormal tumor vasculature can act as a barrier for immune cell migration into tumors. We tested whether targeting IFNgamma and/or TNFalpha into pancreatic neuroendocrine tumors can alleviate immune suppression. We found that intratumoral IFNgamma causes rapid vessel loss, which does not support anti-tumor immunity. In contrast, low-dose TNFalpha enhances T-cell infiltration and overall survival, an effect that is exclusively mediated by CD8(+) effector cells. Intriguingly, lymphocyte influx does not correlate with increased vessel leakiness. Instead, low-dose TNFalpha stabilizes the vascular network and improves vessel perfusion. Inflammatory vessel remodeling is, at least in part, mediated by tumor-resident macrophages that are reprogrammed to secrete immune and angiogenic modulators. Moreover, inflammatory vessel remodeling with low-dose TNFalpha substantially improves antitumor vaccination or adoptive T-cell therapy. Thus, low-dose TNFalpha promotes both vessel remodeling and antitumor immune responses and acts as a potent adjuvant for active immunotherapy. |
