Extended Data Fig. 8: PGE2 suppresses myeloid responsiveness to IFN-I.
From: Cancer cells impair monocyte-mediated T cell stimulation to evade immunity
a, Tumor growth of YUMM1.7 (left) and YUMM3.3 (right) RTT in Itgax-Cre (CTRL) (n = 7 mice for YUMM3.3 and n = 8 for YUMM1.7) or CD11cCre(Itgax-Cre)Ptger2−/−/Ptger4fl/fl treated with anti-CD8 to deplete CD8+ T cells (n = 5 mice for YUMM3.3 and n = 6 for YUMM1.7) or isotype control (n = 7 mice for YUMM3.3 and n = 10 for YUMM1.7). b, TME characterization (flow cytometry) of RTT tumors in CD11cCre-Ptger2−/−Ptger4fl/fl mice (KOEP2/EP4) or CD11cCre control mice (CTRL) (n = 8 tumors/group). c, Quantification of Ly6A+ cells after exposing BM-derived Ly6C+ monocytes to conditioned media (CM) from cancer cell lines ± COX1/2 inhibitor (COX1/2i, indomethacin) during media conditioning ± αΙFNAR1 during 48 h of culture (n = 3 biological replicates per condition). d, MFI quantification of AXL, MHC-I and CD86 (flow cytometry) of BM-DCs treated with fresh media (C) or CM from NTT, RTT and RTT IRF3/7 cells for 24 h ± αΙFNAR1 or isotype control (n = 3 biological replicates per condition). e, Heatmap of scaled expression of ISGs in BM-DCs exposed to CM from RTT IRF3/7 treated with COX1/2i (indomethacin) or untreated, in the presence of αΙFNAR1 or isotype control measured by RT-qPCR (n = 4 technical replicates). f, Heatmap of scaled ISG expression in BM-DCs exposed to CM from NTT and RTT treated with MEKi or untreated, in the presence of αΙFNAR1 or isotype control (n = 4 technical replicates) measured by RT-qPCR. g, Scheme outlining the culture of human monocyte models to CM from cancer cell lines ± COX1/2i during media conditioning (left) and heatmaps of scaled ISG expression (right). h, Quantification of AXL+ BM-DCs treated with IFN-β and PGE2 (flow cytometry) (left) (n = 3 biological replicates) and heatmap of scaled ISG expression measured by RT-qPCR (right) (n = 4 technical replicates). Bar graphs and growth curves depict the mean ± s.e.m. Statistical analysis were performed with a two-way ANOVA with Tukey’s multiple comparisons test in a, a two-tailed unpaired student’s t-test (APCs, cDC1 and infl.monocytes) and two-tailed Mann Whitney U (total cDCs and infl.cDC2s) in b, one-way ANOVA with Tukey’s multiple comparison in c, d and h. ns = not significant.
