Format

Send to

Choose Destination
Nat Genet. 2018 Sep;50(9):1271-1281. doi: 10.1038/s41588-018-0200-2. Epub 2018 Aug 27.

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

Author information

1
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
2
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
3
Perlmutter Cancer Center at NYU Langone Medical Center, New York, NY, USA.
4
Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, Würzburg, Germany.
5
Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
6
Massachusetts General Hospital Cancer Center, Boston, MA, USA.
7
Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.
8
Harvard Medical School, Boston, MA, USA.
9
Department of Dermatology, University Hospital, University Duisburg-Essen, Essen, Germany.
10
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. eliezerm_vanallen@dfci.harvard.edu.
11
Broad Institute of MIT and Harvard, Cambridge, MA, USA. eliezerm_vanallen@dfci.harvard.edu.

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.

PMID:
30150660
PMCID:
PMC6119118
[Available on 2019-02-27]
DOI:
10.1038/s41588-018-0200-2

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center