Effects of tumor mutation burden on the antigen presentation pathway

AbstractTumor mutation burden (TMB) is used to select patients to receive immune checkpoint inhibitors (ICIs) but has mixed predictive capabilities. We hypothesized that inactivation of antigen presenting genes (APGs) that result from increased TMBs would result in inherent resistance to ICIs. We observed that somatic mutations in APGs were associated with increasing TMBs across 9,418 tumor samples of 33 different histological subtypes. In adenocarcinomas of the lung, ITGAX and CD1B were some of the most commonly mutated APGs. In 62 patients with non-small cell lung cancers treated with a PD-1 inhibitor in second or later lines of therapy, there was an association of increased TMB with muta…