Introduction
Treatment with immune checkpoint inhibitors (ICIs) has become extremely
popular owing to its high efficacy and long-term benefits. However, only
a few patients benefit from ICIs because of the cost of ICIs and adverse
events. Therefore, it is important to explore relevant biomarkers. Tumor
mutational burden (TMB), which is defined as the number of somatic
mutations per DNA mega base (Mb), is one of the emerging prognostic
factors to predict the efficacy of immunotherapy, especially ICIs.
Clinical studies1-3 have indicated that patients with
high TMB had better response and survival after the treatment of ICIs in
many cancers than those with a low TMB.
TMB is a novel prognostic biomarker of clinical benefit from ICIs
independent of the PD-L1 level and is currently being prospectively
explored.4,5 In clinical practice, the detection of
TMB is based on whole exon sequencing or targeted next-generation
sequencing of tissue or blood samples. The detected tissues may be from
primary or metastatic lesions. Since the number of mutations in primary
and metastatic lesions is different, it may have some limitations to use
the same standard to predict the prognosis of ICIs for both lesions.
Therefore, in this study, we analyzed the difference in the TMB score
between primary and metastatic lesions in pan-cancer and determined the
difference in cut-offs for guiding ICIs prognosis.