Prevalence of PRKDC mutations and association with response to immune checkpoint inhibitors in solid tumors

Predictive biomarkers of response to immune checkpoint inhibitors (ICI) help to identify cancer patients who will benefit from immunotherapy. Protein kinase, DNA‐activated, catalytic subunit (PRKDC) is an important gene for DNA double‐strand break (DSB) repair and central T‐cell tolerance. We aimed to investigate the association between PRKDC mutations and tumor mutation burden (TMB), tumor microenvironment (TME), and response to ICI. Whole‐exome sequencing data of 4023 solid tumor samples from the Cancer Genome Atlas (TCGA) and panel‐based sequencing data of 3877 solid tumor samples from Geneplus‐Beijing, China, were used to analyze the TMB. The mRNA expression data of 3541 solid tumor samples from TCGA were used to explore the effect of PRKDC mutations on the TME. Four ICI‐treated cohorts were analyzed for verifying the correlation between PRKDC mutations and the response to ICI. In both the TCGA and Geneplus datasets, we found that the TMB in PRKDC mutation samples was significantly higher than in PRKDC wild‐type samples (P
Protein kinase, DNA‐activated, catalytic subunit (PRKDC) is a gene related to DNA damage response (DDR). Here, we found that PRKDC mutation often co‐exists with other DNA damage repair deficiencies and is associated with an increased tumor mutation burden, an inflamed tumor microenvironment, and a good response to immune checkpoint inhibitors.