Review of Immunogenomics and the Role of Tumor Mutational Burden as a Biomarker for Immunotherapy Response

Abstract

Immune checkpoint inhibitors benefit a proportion of patients with cancer, but not all patients nor all histologies will respond to immunotherapy. Therefore, predictive biomarkers are needed. In this review, we outline the ways that lead to hypermutated tumors as well as the potential predictive role of tumor mutational burden (TMB). Findings in selected cancer types suggest that TMB may predict clinical response to immunotherapy, and recently even a prognostic role has been suggested for TMB. An association between high mutational load and clinical benefit was observed in various tumor types; however, it is unclear whether TMB is a strong predictive marker of clinical benefit across all cancers. For that reason, there are still several questions regarding the role of TMB as an immunotherapy biomarker, such as the best measurement technique, the most adequate cutoff, or even whether TMB will be useful for any kind of cancer. We have performed an extensive bibliography research using PubMed with keys words: immunotherapy, tumor mutational load, TMB, immunotherapy biomarkers, and immunotherapy response. In conclusion, TMB has been demonstrated to be a useful biomarker for immunotherapy selection across some cancer types; however, further validation studies are required.

Keywords

• cancer
• immunotherapy
• tumor mutational burden
• tumor mutational load