The predictive efficacy of tumor mutation burden in immunotherapy across multiple cancer types: A meta-analysis and bioinformatics analysis

•The FDA has approved pembrolizumab in all cancers with TMB > 10Mut/Mb based on the findings from the phase 2 KEYNOTE-158 study. However, predictive efficacy of TMB is greeted with many skepticisms.•Cancer patients with high TMB have a better prognosis. Notably, there is no evidence shown whether the good prognosis is caused by the tumor itself or by immunotherapy.•We compared the meta subgroup analysis by tumor types with non-ICIs from TCGA database and found that immunotherapy can increase, not reduce, cancer patients’ OS with high TMB.•TMB is a promising therapeutic and prognostic biomarker for immunotherapy, which indicates a better ORR, DCB, OS and PFS. To explore the predictive efficacy of tumor mutation burden (TMB) as a potential biomarker for cancer patients treated with Immune checkpoint inhibitors (ICIs). We systematically searched PubMed, Cochrane Library, Embase and Web of Science for clinical studies (published between Jan 1, 2014 and Aug 30, 2021) comparing immunotherapy patients with high TMB to patients with low TMB. Our main endpoints were objective response rate (ORR), durable clinical benefit (DCB), overall survival (OS) and progress-free Survival (PFS). Moreover, we downloaded simple nucleotide variation (SNV) data of 33 major cancer types from the TCGA database as non-ICIs group, and compared the high TMB patients’ OS between the non-ICIs group and meta-analysis results. Of 10,450 identified studies, 41 were eligible and were included in our analysis (7713 participants). Compared with low TMB patients receiving ICIs, high TMB yielded a better ORR (RR = 2.73; 95% CI: 2.31–3.22; P = 0.043) and DCB (RR = 1.93; 95% CI: 1.64–2.28; P = 0.356), and a significantly increased OS (HR =0.24; 95% CI: 0.21–0.28; P