What Is Tumor Mutational Burden (TMB)?

Tumor mutational burden (TMB) is a measure of how many mutations exist within a tumor's DNA, and a higher TMB is generally, though imperfectly, associated with better response to checkpoint inhibitor immunotherapy.

TMB is typically reported as the number of mutations per megabase of tumor DNA, measured through genomic sequencing of tumor tissue. The reasoning behind its use as a biomarker is that tumors with more mutations may produce more abnormal proteins, called neoantigens, which can make the tumor more visible to the immune system once checkpoint inhibition removes the tumor's evasion signal.

Research has found that smoking-related lung cancers often have a higher TMB than never-smoker lung cancers, which is one proposed contributing factor — though not the only one — in observed differences in immunotherapy response rates between these two populations.

Like PD-L1 expression, TMB is an imperfect single predictor and is increasingly studied in combination with other biomarkers, including specific co-mutations, to build a more complete picture of which tumors are most likely to respond to a given immunotherapy approach.