RT Journal Article
SR Electronic
T1 Effects of tumor mutation burden on the antigen presentation pathway
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.04.14.439829
DO 10.1101/2021.04.14.439829
A1 Enrique M. Garcia-Rivera
A1 Jiho Park
A1 Aakash Desai
A1 Romain Boidot
A1 Sandy Chevrier
A1 Caroline Truntzer
A1 François Ghiringhelli
A1 Mitesh Borad
A1 Aaron S. Mansfield
YR 2021
UL http://biorxiv.org/content/early/2021/04/14/2021.04.14.439829.abstract
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.