Tumor mutational burden and mismatch repair deficiency discordance as a mechanism of immunotherapy resistance Journal Article

   

Authors:	Bielska, A. A.; Chatila, W. K.; Walch, H.; Schultz, N.; Stadler, Z. K.; Shia, J.; Reidy-Lagunes, D.; Yaeger, R.
Article Title:	Tumor mutational burden and mismatch repair deficiency discordance as a mechanism of immunotherapy resistance
Abstract:	Lynch syndrome is a heritable cancer syndrome caused by a heterozygous germline mutation in DNA mismatch repair (MMR) genes. MMR-deficient (dMMR) tumors are particularly sensitive to immune checkpoint inhibitors, an effect attributed to the higher mutation rate in these cancers. However, approximately 15% to 30% of patients with dMMR cancers do not respond to immunotherapy. This report describes 3 patients with Lynch syndrome who each had 2 primary malignancies: 1 with dMMR and a high tumor mutational burden (TMB), and 1 with dMMR but, unexpectedly, a low TMB. Two of these patients received immunotherapy for their TMB-low tumors but experienced no response. We have found that not all Lynchassociated dMMR tumors have a high TMB and propose that tumors with dMMR and TMB discordance may be resistant to immunotherapy. The possibility of dMMR/TMB discordance should be considered, particularly in less-typical Lynch cancers, in which TMB evaluation could guide the use of immune checkpoint inhibitors. © 2021 Harborside Press. All rights reserved.
Journal Title:	Journal of the National Comprehensive Cancer Network
Volume:	19
Issue:	2
ISSN:	1540-1405
Publisher:	Harborside Press
Date Published:	2021-02-01
Start Page:	130
End Page:	133
Language:	English
DOI:	10.6004/jnccn.2020.7680
PUBMED:	33545685
PROVIDER:	scopus
PMCID:	PMC8356354
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85101008543&doi=10.6004%2fjnccn.2020.7680&partnerID=40&md5=4b2916b4c4430fba23a44bd742a46579
Notes:	Article -- Export Date: 1 March 2021 -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/177445