Here we report through systematic cancer genomics and transcriptomic association studies that APOBEC3B overexpression is associated with immune gene expression and known immunotherapy response biomarkers, APOBEC mutational signature is specifically enriched in patients with durable clinical benefit (DCB) after immunotherapy and APOBEC mutation count can be better than total mutation count in predicting immunotherapy response. The gene discussed is APOBEC3B; the disease is cancer.