Tumor mutational burden: why is it still a controversial agnostic immunotherapy biomarker?

For the past few years, researchers and oncologists have been pushing to find biomarkers that would help predict which treatment option would best work on a patient. Tumor Mutational Burden (TMB) is one of the latest biomarkers that is being studied and considered as a promising agnostic immunotherapy biomarker. However, it still shows controversial results in studies due to the difficulty in finding solid comparable results. This is a consequence of different cutoff definitions among many cancer types, age ranges, and the use of different sequencing assays, in addition to its association with other biomarkers such as PD-L1. Finally, the use of composite biomarkers to assess the genetic signature of a tumor might be the way forward to seriously use TMB as an agnostic biomarker.