Fig. 7. In vivo paclitaxel response relies on STING and is amplified by sequential use of BH3 mimetics.

a Control or STING^−/− MDA-MB-231 cell lines were injected in mammary fat pad in immunodeficient mice and when tumors reached about 100 mm³, paclitaxel has been injected twice at D0 and D9 and tumors were calipered every day (n = 5 mice per group). b Immunoblot (left panel) and qPCR (right panel) analysis of indicated markers in tumors from a. c–d Same experiment as (a) using control and cGAS ^−/−(c) or TNFα^−/−(d) MDA-MB-231 cells (n = 5 mice per group). e Therapeutical protocols using paclitaxel and ABT-263 combinations (left panel) applied to control or STING^−/− MDA-MB-231 xenograft model (left panel), tumor volume (mean and SEM) in each mice groups (middle panel) and histogram showing the average tumor size at the end of the experiment (right panel). n = 6 mice per group. f Annexin V assay in MDA-MB-468 after 48 h treatment with the STING agonist diABZI plus WEHI-539, ABT-199, or paclitaxel or not. g–h Same experiment as in f using control, STING^−/−, NOXA^−/−, or TNFα^−/− (g) or IκBαSR (NF-κB super repressor) (h) MDA-MB-468 cells, treated by diABZI plus WEHI-539 or not. i NOXA immunoblot analysis after a 48 h diABZI treatment in MDA-MB-468 cells. j Cell viability of PDO after diABZI treatment in presence of ABT-737 or not. k Tumor volume in the same xenograft model as in a upon sequential treatment with diABZi (2×/week) plus Navitoclax (2×/week) as indicated (n = 5 mice per group). Error bars indicate mean +/− SEM; Two-sided unpaired t-test. The symbols correspond to a p-value inferior to *0.05 and **0.01. NS: not significant.