Evaluation of POLE/POLD1 Variants as Potential Biomarkers for Immune Checkpoint Inhibitor Treatment Outcomes

To the Editor A recent study published by Wang et al¹ evaluated POLE/POLD1 variants as potential biomarkers for immune checkpoint inhibitor (ICI) treatment outcomes in multiple cancer types using the cBioPortal database (https://www.cbioportal.org). The authors conclude that “mutations in all exons of these 2 genes should be integrated into predictive biomarker panels for ICI therapy.”¹ However, this interpretation may be incorrect considering that not all POLE/POLD1 variants are oncogenic and therefore would not result in a high tumor mutation burden (TMB).