PT  - JOURNAL ARTICLE
AU  - Enrique M. Garcia-Rivera
AU  - Jiho Park
AU  - Aakash Desai
AU  - Romain Boidot
AU  - Sandy Chevrier
AU  - Caroline Truntzer
AU  - François Ghiringhelli
AU  - Mitesh Borad
AU  - Aaron S. Mansfield
TI  - Effects of tumor mutation burden on the antigen presentation pathway
AID  - 10.1101/2021.04.14.439829
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.04.14.439829
4099  - http://biorxiv.org/content/early/2021/04/14/2021.04.14.439829.short
4100  - http://biorxiv.org/content/early/2021/04/14/2021.04.14.439829.full
AB  - Tumor 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 mutations in APGs; however, mutations in one or more APGs were associated with improved progression-free survival. Contrary to our hypothesis, mutations in APGs were associated with improved progression-free survival with nivolumab, possibly due to the involvement of single alleles rather than complete loss.Competing Interest StatementThe authors have declared no competing interest.