Landscape of tumor mutation load, mismatch repair deficiency, and PD-L1 expression in a large patient cohort of gastrointestinal cancers

Purpose: The efficacy of immunotherapy varies widely among different gastrointestinal cancers. Response to immune checkpoint inhibitors is shown to correlate with tumor mutation load (TML), mismatch repair deficiency status (dMMR), and programmed cell death-ligand 1 (PD-L1) expression. Herein, we attempt to quantify TML, dMMR, and PD-L1 expression and determine their interrelationship in gastrointestinal cancers. Experimental Design: A total of 4125 tumors from 14 different gastrointestinal cancer sites were studied. Next-generation sequencing was performed on genomic DNA isolated from formalin-fixed paraffin-embedded (FFPE) tumor samples using the NextSeq platform. TML was calculated using only somatic nonsynonymous missense mutations sequenced with a 592-gene panel. Microsatellite instability (MSI) was assessed by validated direct analysis of altered known MSI loci in the target regions of the sequenced genes. PD-L1 expression was analyzed by immunohistochemistry. Results: Right-sided...