Fig. 6: Targeting the immune microenvironment abrogates Brd7-deficient breast cancer metastatic outgrowth in lung. | Nature Communications

Fig. 6: Targeting the immune microenvironment abrogates Brd7-deficient breast cancer metastatic outgrowth in lung.

From: Brd7 loss reawakens dormant metastasis initiating cells in lung by forging an immunosuppressive niche

Fig. 6: Targeting the immune microenvironment abrogates Brd7-deficient breast cancer metastatic outgrowth in lung.

A, B Mice were treated with anti-Ly6G (300 µg/mice) or isotype control antibody every other day starting 5 days prior to injection with either 4T07 control or 4T07 Brd7 KO cells (Brd7 KO-Anti-Ly6G, N = 9 mice;Brd7 KO-IgG, N = 8 mice; 4T07-TGL-Anti-Ly6G,N = 8 mice; 4T07-TGL-IgG,N = 8 mice). Representative bioluminescence images for the indicated murine cohorts at 30 min, 2 weeks, and 4 weeks post tumor cell injection (A). Line graph showing normalized photon flux for the indicated murine cohorts over time (B). ****p < 0.0001. Statistical analysis by unpaired two-tailed Mann-Whitney test; error bars represent SEM. C Experiment design of neutrophil/cancer cell co-culture and NET quantification. D NET extracellular DNA quantification by Sytox Orange fluorescence for the indicated co-cultures. (**p < 0.01; N = 6) Statistical analysis by unpaired two-tailed t test; in all panels, error bars represent SEM. E, F Mice were treated with the NET inhibitor Sivelestat or vehicle every other day starting 5 days prior to injection with either 4T07 control or 4T07 Brd7 KO cells (Brd7 KO-Vehicle treatment, N = 10;Brd7 KO-Sivelestat treatment, N = 10). Represent bioluminescence images for the indicated murine cohorts at 30 min, 1 week, and 4 weeks post tumor cell injection (E). Line graph showing the normalized photon flux for the indicated murine cohorts over time (F). ****p < 0.0001. Statistical analysis by unpaired two-tailed Mann-Whitney test; error bars represent SEM. G, H Mice were treated with isotype control, Anti-LAG3, Anti-CTLA4, or both Anti-LAG3 and Anti-CTLA4 every other day starting 1 day after cancer cell injection until Week 5 (Brd7 KO-Anti-LAG3, N = 10 mice;Brd7 KO-Anti-CTLA4, N = 10 mice; 4T07-TGL-Anti-LAG3 + CTLA4, N = 10 mice; 4T07-TGL-Brd7 KO-IgG, N = 10 mice). Representative bioluminescence images for the indicated murine cohorts at 30 min, 2 weeks, and 5 weeks post tumor cell injection (G). Line graph showing the normalized photon flux for the indicated murine cohorts over time (H). ****p < 0.0001. Statistical analysis by unpaired two-tailed Mann-Whitney test; error bars represent SEM. I Kaplan-Meier survival analysis for the indicated murine cohorts. Statistical analysis by log-rank test. ***p < 0.001, ns, not significant. J Schematic of the mechanism(s) governing BRD7-deficient breast cancer lung metastatic outgrowth. 95% CI was used to analyze the results unless mentioned otherwise. Source data are provided as a Source Data file.

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