Fig. 4: OVT limits, in a monocyte-depended fashion, neutrophil antiviral activity within infected tumors. | Communications Biology

Fig. 4: OVT limits, in a monocyte-depended fashion, neutrophil antiviral activity within infected tumors.

From: Repeated dosing improves oncolytic rhabdovirus therapy in mice via interactions with intravascular monocytes

Fig. 4

MIP-2 response in tumor interstitial fluid (a) and blood (b) to a single or repeated VSV treatment at 56 h following single VSV treatment or 8 h following a second i.v. injection of VSV (106 PFU) ± CLL 24 h post first virus administration; mean ± SEM; n = 4 (one-way ANOVA followed by Tukey’s multiple comparisons test). c Time-lapse images of VSV-infected (green) and uninfected regions of a CT26LacZ tumor (red); neutrophils (magenta); vessels (Qtracker 655, gray); scale bar, 100 µm. d FC analysis of intratumor neutrophils 72 h following a single VSV dose or 24 h post second VSV dose (106 PFU) ± 20 µg anti-CCR2 24 h after initial virus administration; mean ± SEM; n = 3 (one-way ANOVA followed by Tukey’s multiple comparisons test). e IVM analysis of neutrophils behavior 72 h following a single VSV dose or 24 h post second VSV dose (106 PFU) ± anti-CCR2 24 h after initial virus administration; mean ± SEM (two-way ANOVA followed by Sidak’s multiple comparisons test). f IVM quantification of neutrophil-monocyte interactions following single and repeat dosing of VSV ± anti-CCR2 treatment; mean ± SEM; n = 8 (one-way ANOVA followed by Tukey’s multiple comparisons test). g Representative IVM image of neutrophils (green) interacting with virus (blue) bound monocytes (red). The insert shows individual channels for the ROI (dotted yellow box). Scale bar, 25 µm. h Luminescence intensity for CT26LacZ tumors following single dose OVT treatment (106 PFU VSV-FLUC i.v.) ±anti-Ly6g 24 h after virus administration; results are shown as mean with individual values (n = 7); two-way ANOVA followed by Sidak’s multiple comparisons test. i, k Tumor measurements for CT26LacZ-bearing mice treated with one (i) or two (k) doses of VSV-FLUC (106 PFU, 48 h between i.v. injections) ± anti-Ly6G 24 h after the first dose of VSV; mean ± SEM (n = 7 for single dose, n = 10 for multiple dose groups); two-way ANOVA. j, l. Kaplan-Meier survival plots for mice treated with one (j) or two (l) doses of VSV-FLUC ± anti-Ly6G (n = 7 for single dose, n = 15 for multiple dose groups); log-rank test.

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