Extended Data Fig. 8: Role of the STING and SREBP1 pathways on the Olaparib-induced macrophage phenotype.
CD14+ cells from healthy human donors were isolated and differentiated to mature myeloid cells with IL-4 and GM-CSF for 5 days in the presence or absence of Olaparib and then collected for immunophenotyping by flow cytometry. a-e, A STING inhibitor or a SREBP1 inhibitor (fatostatin) was added to the ex vivo macrophage differentiation assay for 5 days, cells were collected and then analyzed by flow cytometry. f, A STING agonist was added to differentiating myeloid cells 24 hours before flow cytometry analysis. The STING agonist did not affect the viability or proportion of CD45+, CD14+, CD163+, or CSF-1R+ cells of the differentiated myeloid cells but did increase CD80+, PD-L1+ and pTBK1 expression on CD11b+ cells. Statistical analysis was performed using unpaired one-tailed t-test for subfigure f and One-way ANOVA with Uncorrected Fisher’s LSD for subfigure a-e. Error bars represent standard error of the mean (±SEM) with 3-7 healthy human donors per group, as shown. Exact p values indicated in each panel for each comparison. g-l, Bone marrow cells from wild-type and sting-/- mice was isolated and differentiated to mature myeloid cells as described above in presence or absence of Olaparib and immunophenotyping by flow cytometry was performed. Olaparib-induced phenotypes were independent of STING. Statistical analysis was performed using One-way ANOVA with uncorrected Fisher’s LSD. Error bars represent standard error of the mean (±SEM) with n = 5 mice per group. Exact p values indicated in each panel for each comparison.
