Figure 5 from Tumoral Interferon Beta Induces an Immune-Stimulatory Phenotype in Tumor-Associated Macrophages in Melanoma Brain Metastases

Irradiation induces the proinflammatory type I IFN-response signature in TAM associated with increased overall survival in patients with melanoma brain metastases. A, Heatmap of normalized gene counts of the myeloid type I IFN-response signature in previously irradiated MBM not expressing the myeloid type I IFN-response signature (neg., negative) compared to MBM expressing the myeloid type I IFN-response signature (pos., positive; n = 12 and n = 9). B, GSEA of a curated M1 phenotypic marker gene set in MBM from non-irradiated patients compared to MBM from previously irradiated patients. Enrichment Score = 0.55, NES = 2.06, adjusted P value = 1.9e–8 (n = 48 and n = 21). C and D, Deconvolution of TAM abundances in previously irradiated MBM not expressing the myeloid type I IFN-response signature (neg.) compared to MBM expressing the myeloid type I IFN-response signature (pos.) using CIBERSORTx (n = 12 and n = 9). Displayed as absolute proportion of each cell type in each sample in C or mean percentage per group and M1/M2 ratio in D. E, Kaplan–Meier survival estimates for the association of type I IFN-signature expression with the overall survival of irradiated MBM patients (n = 12 and n = 9). For the M1 phenotypic marker gene set see Supplementary Table S3. Data are expressed as individual values for A, median + IQR and individual values for C and mean for D. Statistical significance was determined by paired t test for C and log-rank test for E.