Fig. 2: Relationship between somatic mutations and the response to ICI. | Nature Communications

Fig. 2: Relationship between somatic mutations and the response to ICI.

From: Predicting immunotherapy response of advanced bladder cancer through a meta-analysis of six independent cohorts

Fig. 2

A Responders have a higher tumor mutational burden (Z score TMB) than non-responders (median Z score TMB R = 0.18, NR = −0.45). TMB is calculated as the number of non-synonymous mutations per 50 Mb. The differences were highly significant (two-sided, two-sample Wilcoxon test, p value = 2.1e-13). B Responders show a higher mean TMB than non-responders. This finding is consistent over all six datasets, and four of the six datasets display significant differences (two-sided, two-sample Wilcoxon test). C The difference between treatment response groups remains when separating the TMB into clonal and subclonal by a cancer cell fraction (CCF) cutoff of 0.9 (two-sided, two-sample Wilcoxon test). Median clonal TMB R: 2.15 mut/50 Mb, NR: 1.1 mut/50 Mb; median subclonal TMB R: 1.19 mut/50 Mb, NR: 0.8 mut/50 Mb. D Responders are significantly enriched in APOBEC-induced mutations compared to non-responders (two-sided, two-sample Wilcoxon test, p value = 9e-04; median APOBEC-enrichment score R: 3.45, NR: 2.85). E Spearman correlation between different DNA-derived variables. F Number of non-synonymous mutations by type and association of the different mutation types with response. Missense mutations, nonstop mutations, and putative neoantigens were found to be significantly associated with the response (two-sided, two-sample Wilcoxon test). Medians for number of missense mutations R: 202 muts, NR: 88 muts; nonstop mutations R: 0 muts, NR: 0 muts, frameshift insertions/deletions R: 3 muts, NR: 3 muts; in-frame insertions/deletions R: 0 muts, NR: 0 muts; putative neoantigens R: 22.5 neoantigens, NR: 12 neoantigens. Neoantigens were predicted from missense mutations applying a threshold of 500 nM IC50 binding affinity in NetMHCpan 4.0. N = 234 patients. R responders (yellow), NR non-responders (turquoise), TMB tumor mutational burden, INDELs insertions and deletions. All p values are indicated in the according plots. Source data are provided as a Source Data file.

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