Fig. 6

Pharmacological manipulation of DLL1 or Jag1-mediated signaling reduces tumor growth and improves anti-tumor immunity. a, b Enhancement of DLL1 signaling using multivalent clustered DLL1 overcomes the critical dendritic cell DLL1 deficiency and restricts tumor growth. Growth of LLC tumor (a) and MT5 pancreatic tumor (b) in wild-type and DC-specific Dll1^−/− mice. Mice were treated with 0.2 mg/kg body weight of multivalent clustered DLL1-Fc fusion protein every 2 days for 20 days. Mean ± SEM, 8 mice per group; *, p < 0.05; **, p < 0.01. c, d Treatement with soluble fragment of extracellular domain of JAG1 (sJAG1) significantly reduces tumor growth and improves survival of tumor-bearing mice. LLC tumor growth (c) and log-rank survival curves (d) in mice treated with monovalent soluble JAG1 construct, 1 mg/kg body weight, i.p. every 2 days for 20 days. Percentage of FoxP3⁺ cells among CD4⁺ cells (e) and IFN-g ELISPOT (f) for splenocytes in mice treated with soluble JAG1 on day 18 after LLC tumor initiation. Mean ± SEM, 8–10 mice per group; *, p < 0.05; **, p < 0.01