Fig. 5: Maraviroc enhances neoantigen vaccine immunity by blocking moDC migration to draining lymph nodes.

a, UMAP visualization of Ccr5, Ccl5 and Ccr7 expression in myeloid cells as in Fig. 1a. b, Xenium spatial transcriptomics expression of Cd19, Cd3e and Ccl5 in the lung-draining lymph nodes from C57BL/6 WT mice on day 16 post-intravenous injection of 4 × 10⁵ KPAR1.3 adenocarcinoma cells. Scale bar, 100 µm. c, Representative lung images (left) and quantification of surface metastases (right) in lethally irradiated C57BL/6 WT mice reconstituted with Ccr2^−/−:WT (80:20) or Ccr2^−/−:Ccr5^−/− (80:20) BM on day 16 post-intravenous injection with B16F10 melanoma cells. One of two independent experiments with n  = 5 mice per group is shown. Statistical significance was determined via a Student’s two-tailed t-test with P < 0.0001. d, Representative H&E staining (left) and quantification of the number of tumors per section (right) in the lungs of Ccr2^−/−:WT (80:20) (n = 5) and Ccr2^−/−:Ccr5^−/− (80:20) (n = 4) mixed BM chimeras as in c on day 16 post-intravenous injection with KPAR adenocarcinoma cells. Two independent experiments were conducted. Statistical significance was determined via a Student’s two-tailed t-test with P < 0.0001. e, Representative flow cytometry plots showing the gating strategy for the identification of antigen (Ag)⁺ Ly6C⁺ moDCs and CD26⁺ DCs (top, left to right) and quantification of the frequency of Ag⁺ monocytes (bottom right) in the lung-draining lymph nodes of WT mice treated with or without 500 μg maraviroc 3 h before intranasal administration of 5 μg OVA Ag + 50 μg poly(I:C) (top and middle) or nondraining distal skin lymph nodes from mice receiving 5 μg OVA Ag + 50 μg poly(I:C) without maraviroc (bottom) and analyzed 24 h post-antigen administration. Three independent experiments were conducted with n  = 4 per group. Statistical significance was determined via a Student’s two-tailed t-test with P < 0.0001. f, Schematics showing the experimental flow (top), representative lung images (middle) and number of surface metastases per lung (bottom) in WT mice treated with PBS (n = 5), neoantigen (NeoAg) peptides (n = 5), NeoAg peptides + poly(I:C) (n = 4) or NeoAg peptides + poly(I:C) + maraviroc (n = 5) on day 14 and 7 before intravenous injection with B16F10 melanoma cells and analyzed on day 16 post-tumor injection. Two independent experiments were conducted. Statistical significance was determined via one-way ANOVA followed by Bonferroni’s multiple comparison test with P = 0.0035 (NeoAg + poly(I:C) versus NeoAg + poly(I:C) + maraviroc). All data are represented as mean ± s.e.m. **P < 0.01; ***P < 0.001; ****P < 0.0001.

Source data