Fig. 3: Cancer cells produce PGE2 and downregulate IFN-I responses to confer immunotherapy resistance.
From: Cancer cells impair monocyte-mediated T cell stimulation to evade immunity
a, Pathway enrichment analysis of differential gene expression in cancer cells isolated from YUMM1.7OVA NTT tumours and RTT tumours (n = 3 tumours per group; Supplementary Table 3). Adjusted P values were computed using the Benjamini–Hochberg correction. b, PGE2 ELISA of YUMM1.7OVA tumours in Rag2–/– mice (n = 10 NTT, n = 11 RTT CTRL, n = 7 RTT Ptgs1/2 KO over 2 independent experiments). c, Top, representative BLI image of T cells 96 h after ACT (key as in Fig. 1b). Bottom, BLI quantification (n = 4 mice NTT, n = 6 mice RTT CTRL and RTT Ptgs1/2 KO). d, Left, response of YUMM1.7OVA tumours in Rag2–/– mice to ACT (n = 7 mice per group). Right, YUMM3.3 in C57BL/6 mice (n = 5 mice per group). e, IFNβ ELISA of supernatants from YUMM1.7OVA NTT and RTT cells (n = 5 replicates per group over 2 independent experiments). f, Top, representative BLI images of T cells in YUMM1.7OVA RTT CTRL and RTT IRF3/7 tumours in Rag2–l– mice 96 h after ACT (key as in Fig. 1b). Bottom, BLI quantification (n = 6 mice per group). g, Left, response of YUMM1.7OVA tumours in Rag2–/– mice to ACT (n = 4 mice RTT CTRL, n = 5 mice RTT IRF3/7). Right, YUMM3.3 in C57BL/6 mice (n = 6 mice per group). h, Response to ACT of YUMM1.7OVA RTT Ptgs2 KO (left) and RTT IRF3/7 tumours (right) in Rag2–/– (n = 4 mice per group) and Batf3–/–Rag2–/– mice (n = 5 mice per group). i, PGE2 and IFNβ ELISAs of NTT and RTT A375 human melanoma (n = 2 replicates per group for PGE2, n = 3 tumours per group for IFNβ). Arrows in d, g and h indicate day of ACT. Bar graphs depict the mean ± s.e.m. Statistical analysis was performed with a two-tailed unpaired Student’s t-test (e,f,i) or one-way ANOVA with Tukey’s multiple comparisons test (b,c).
