Fig. 1: Mutational landscape of immune checkpoint blockade (ICB) resistant melanoma.
From: Molecular patterns of resistance to immune checkpoint blockade in melanoma
A Tumor mutational burden (TMB) calculated as total number of somatic mutations in n = 20 anti-CTLA4 resistant (CTLA4res) or n = 17 anti-PD1 resistant tumors (PD1res) as compared to n = 68 ICB naïve distant metastases from the Cancer Genome Atlas (TCGA) n = 68. Boxplot is displayed with the center-line as median, the box limits as lower and upper quartiles, and with whiskers covering the most extreme values within 1.5 x Interquartile-Range. B Genetic aberrations of selected genes in CTLA4res (n = 17) and PD1res (17) resistant melanomas, combining mutation-, copy number- and HLA Loss-of-Heterozygosity (LOH) levels. The majority of PD1res melanomas had previously relapsed on CTLA4 blockade. Tumor mutational burden and mutational signatures are indicated on top. Frequencies of activating events for potential oncogenes and loss-of-function events for potential tumor suppressor genes are depicted on the right for ICB resistant tumors excluding mucosal samples, and for the ICB naïve TCGA control cohort, respectively, and significant differences are indicated by * (BRAF P = 3 × 10−4 and NF1 P = 0.008, Fisher test). All test were two-sides. Three mucosal melanomas are displayed in heatmap but excluded from statistical analyses. C Genetic alterations of genes in the interferon gamma and MHC-I pathways between CTLA4res (n = 17) and PD1res (n = 17). The frequency of combined events is noted for each gene. Annotation and event legends as in B. D Frequency plot of immune regulatory pathways in CTLA4res (n = 17) and PD1res (n = 17) melanomas, considering only loss-of-function events. Amp Amplification. Del Deletion. Source data and exact p-values are provided as a Source Data file.
