Fig. 7: Blockade of LTβR-nonclassical NF_ΚB inhibits tumor growth, immune suppressive cell recruitment, and tumor angio- and lymphangiogenesis.

a, b Intradermally transferred B16F10 melanoma in C57BL6 mice treated with an intratumoral or peritumoral injection of 10 nmol per tumor of nciLT, ciLT, or CP for 5 days. Scheme of tumor treatment (a). Tumor growth (b), ten mice in each cohort except for the nciLT-treated group (n = 12). p values are calculated by comparing each peptide-treated group to the PBS group at days 7, 10, 13, 16, and 20 using an unpaired two-tail t-test. **** p < 0.0001, ** p = 0.0045 (nciLT and ciLT day 10); p = 0.008 (ciLT day 16), *p = 0.0405. c, d At day 13, tumors (n = 4) analyzed for CD4, CD8, Foxp3⁺ CD4 Tregs and T cell IFNγ (c), Ly6G⁺CD11b⁺ MDSCs, CXCL1, and CXCL10 expression in CD45⁻ CD31⁻PDPN⁻ cells or Lyve-1⁺ PDPN⁺ LECs (d) by flow cytometry. Some samples were measured two more times in separate staining procedures to reach the accuracy (CD4, CD8, CXCL10, and MDSC). Gating strategy shown (c, d). e, f At day 20, tumors were assessed for angiogenesis (CD31⁺/Lyve-1⁻) and lymphangiogenesis (CD31⁺/Lyve-1⁺) by immunohistochemistry and analyzed for SOX18 (e) and FLRT2 (f). Representative of eight images of each group. Magnification 20x, scale bar:42 μm. g, h Expression on CD31⁺/Lyve-1⁺ lymphatic vessels and CD31⁺/Lyve-1⁻ blood vessels of tumors (n = 5). MFIs (g) and quantification of co-localization between SOX18 or FLRT2 and lymphatic or blood vessels (h). Representative of 2 (a–h) independent experiments shown. c–h: Mean ± SEM. *p = 0.0116, **p = 0.0019, ***p = 0.0005, ****p < 0.0001 by one-way ANOVA. Source data are provided as a Source Data file.