You are here

Nat Genet DOI:10.1038/s41588-018-0200-2

Genomic correlates of response to immune checkpoint blockade in microsatellite-stable solid tumors.

Publication TypeJournal Article
Year of Publication2018
AuthorsMiao, D, Margolis, CA, Vokes, NI, Liu, D, Taylor-Weiner, A, Wankowicz, SM, Adeegbe, D, Keliher, D, Schilling, B, Tracy, A, Manos, M, Chau, NG, Hanna, GJ, Polak, P, Rodig, SJ, Signoretti, S, Sholl, LM, Engelman, JA, Getz, G, Jänne, PA, Haddad, RI, Choueiri, TK, Barbie, DA, Haq, R, Awad, MM, Schadendorf, D, F Hodi, S, Bellmunt, J, Wong, K-K, Hammerman, P, Van Allen, EM
JournalNat Genet
Volume50
Issue9
Pages1271-1281
Date Published2018 Sep
ISSN1546-1718
Abstract

Tumor mutational burden correlates with response to immune checkpoint blockade in multiple solid tumors, although in microsatellite-stable tumors this association is of uncertain clinical utility. Here we uniformly analyzed whole-exome sequencing (WES) of 249 tumors and matched normal tissue from patients with clinically annotated outcomes to immune checkpoint therapy, including radiographic response, across multiple cancer types to examine additional tumor genomic features that contribute to selective response. Our analyses identified genomic correlates of response beyond mutational burden, including somatic events in individual driver genes, certain global mutational signatures, and specific HLA-restricted neoantigens. However, these features were often interrelated, highlighting the complexity of identifying genetic driver events that generate an immunoresponsive tumor environment. This study lays a path forward in analyzing large clinical cohorts in an integrated and multifaceted manner to enhance the ability to discover clinically meaningful predictive features of response to immune checkpoint blockade.

DOI10.1038/s41588-018-0200-2
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/30150660?dopt=Abstract

Alternate JournalNat. Genet.
PubMed ID30150660
PubMed Central IDPMC6119118
Grant ListK08 CA188615 / CA / NCI NIH HHS / United States