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

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.

journal_name

Nat Genet

journal_title

Nature genetics

authors

Miao 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,Chouei

doi

10.1038/s41588-018-0200-2

subject

Has Abstract

pub_date

2018-09-01 00:00:00

pages

1271-1281

issue

9

eissn

1061-4036

issn

1546-1718

pii

10.1038/s41588-018-0200-2

journal_volume

50

pub_type

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