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. 2022 Jun 27;13:3671. doi: 10.1038/s41467-022-31238-y

Fig. 1. MYC predicts poor response to immune checkpoint inhibitors.

Fig. 1

a Average tumor volume for MTB/TOM tumors treated with anti-PD-L1 or isotype antibody while fed doxycycline chow (MYC-ON state). Mean ± S.E.M; two-sided unpaired t-test on day 8, isotype (n = 3), anti-PD-L1 (n = 4). b Survival (ethical tumor endpoint, length: 20 mm). Log rank test, isotype (n = 4), anti-PD-L1 (n = 8). c Average tumor volumes for animals bearing MC38-vector tumors. Mean ± S.E.M, two-sided unpaired t-test tumor volume on day 15 (isotype n = 8, anti-PD-L1 n = 10). d Average tumor volumes for animals bearing MC38-MYC tumors. Mean ± S.E.M, two-sided unpaired t-test tumor volume on day 15 (n = 6/treatment). e Individual tumor volumes graphed during doxycycline chow removal (MYC-OFF) and either anti-PD-L1 (n = 8) or isotype control antibody (n = 9). f Survival (ethical study endpoint). MYC-OFF + isotype antibody (n = 9) and MYC-OFF + anti-PDL1 (n = 8). Log rank test. g Top: Representative flow cytometry plots. PD-L1 expression (red) or isotype antibody (gray) displayed as percent of maximum (modal). Bottom: Bar graphs displaying average geometric mean fluorescence intensity (GMFI) for PD-L1 in each population. n = 6 tumors analyzed for each cell type, except for CD11c (n = 3), mean ± S.E.M., unpaired t-test. hj Scatterplots of h CD274, i tumor infiltrating leukocytes (TIL), and j IL2/STAT5 Hallmark gene signature against the MYC_BC signature in the TCGA TNBC cohort (n = 158). Pearson’s coefficient (Rp), adjusted p-value (Benjamini–Hochberg FDR corrected). k Evaluation of IL2/STAT5 Hallmark gene signature against the MYC_BC signature in METABRIC. ρ, Spearman’s r and exact p-value displayed. l Evaluation of IL2/STAT5 Hallmark gene signature against the MYC_BC signature in the TONIC Trial. ρ, Spearman’s r and exact p-value displayed. m Kaplan–Meier curves of event-free survival for patients with HER2 negative and hormone receptor (HR) negative tumors treated on the Pembrolizumab arm of the I-SPY 2 TRIAL dichotomized by MYC_BC signature. Cox proportional hazard (PH) modeling. n, o Survival analysis correlating MYC expression from pre-treatment tumors pulled out of the TIDE database using Cox PH z-scores: n Kaplan–Meier curves of overall survival in patients with metastatic urothelial carcinoma from Mariathasan et al., 2018 and o Kapaln–Meier curves of overall survival in patients with metastatic clear cell renal cell carcinoma (ccRCC) from Miao et al., 2018. Source data are provided in the Source Data file. Source data for panel l provided at EGA (EGAS00001003535).