| First Author | Johansson-Percival A | Year | 2017 |
| Journal | Nat Immunol | Volume | 18 |
| Issue | 11 | Pages | 1207-1217 |
| PubMed ID | 28892469 | Mgi Jnum | J:259570 |
| Mgi Id | MGI:6142005 | Doi | 10.1038/ni.3836 |
| Citation | Johansson-Percival A, et al. (2017) De novo induction of intratumoral lymphoid structures and vessel normalization enhances immunotherapy in resistant tumors. Nat Immunol 18(11):1207-1217 |
| abstractText | The tumor microenvironment confers profound resistance to anti-cancer immunotherapy. By targeting LIGHT, a member of the TNF superfamily of cytokines, to tumor vessels via a vascular targeting peptide (VTP), we developed a reagent with the dual ability to modulate the angiogenic vasculature and to induce tertiary lymphoid structures (TLSs). LIGHT-VTP triggered the influx of endogenous T cells into autochthonous or syngeneic tumors, which are resistant to immunotherapy. LIGHT-VTP in combination with checkpoint inhibition generated a large number of intratumoral effector and memory T cells with ensuing survival benefits, while the addition of anti-tumor vaccination achieved maximal therapeutic efficacy. Thus, the combination treatments stimulated the trafficking of pre-existing endogenous effector T cells as well as their intratumoral activation and were more successful than current immunotherapies, which fail due to tumor-intrinsic resistance mechanisms. |
