High tumor mutational burden predicts survival and responses to ICI immunotherapy in a cancer-dependent manner

Objective High tumor mutational burden (TMB) is a promising biomarker for patients with immunotherapy in certain types of solid tumors. This article focuses on exploring possible universally optimal cutoffs of TMB for predicting immune checkpoint inhibitors (ICIs) response and prognosis for eight types of cancers. Methods The present study collected eight types of tumors including 2767 patients receiving immune checkpoint inhibitors (ICIs) treatment and 14862 patients without ICI treatment. We tried to explore optimal cutoffs of TMB in each type of tumor via selecting several possible cutoffs of TMB including 10mut/Mb, top 10%, 20%, and 30% of TMB within each histology. Results We found that there was a significant difference in TMB values between ICI-treated and non-ICI-treated groups. The cutoff of TMB appropriate for predicting response rates, progression rates, and survival rates was varied in ICI therapy patients. Moreover, the optimal cutoff of TMB for predicting progression-free survival and overall survival in different types of the tumor was also quietly different. Conclusion Our current study suggested that TMB predicts prognosis and responses to ICI treatment in a cancer-dependent manner. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This research was supported by the National Natural Science Foundation of China (No.82273328), and the Translational Medicine Research Fund of Zhongnan Hospital of Wuhan University (ZLYNXM202011). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes * TMB : Tumor mutational burden ICIs : Immune checkpoint inhibitors PD-1 : Programmed death 1 PD-L1 : Ligand of the PD-1 axis CTLA4 : Cytotoxic T lymphocyte antigen 4 FDA : United States Food and Drug Administration PFS : Progression-free survival OS : Overall survival MSI-H : high microsatellite instability