Format

Send to

Choose Destination
Nat Med. 2019 Mar;25(3):389-402. doi: 10.1038/s41591-019-0382-x. Epub 2019 Mar 6.

Genomic correlates of response to immune checkpoint blockade.

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
Department of Immunology, Harvard Medical School, Boston, MA, USA.
4
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Eliezerm_vanallen@dfci.harvard.edu.
5
Broad Institute of MIT and Harvard, Cambridge, MA, USA. Eliezerm_vanallen@dfci.harvard.edu.

Abstract

Despite impressive durable responses, immune checkpoint inhibitors do not provide a long-term benefit to the majority of patients with cancer. Understanding genomic correlates of response and resistance to checkpoint blockade may enhance benefits for patients with cancer by elucidating biomarkers for patient stratification and resistance mechanisms for therapeutic targeting. Here we review emerging genomic markers of checkpoint blockade response, including those related to neoantigens, antigen presentation, DNA repair, and oncogenic pathways. Compelling evidence also points to a role for T cell functionality, checkpoint regulators, chromatin modifiers, and copy-number alterations in mediating selective response to immune checkpoint blockade. Ultimately, efforts to contextualize genomic correlates of response into the larger understanding of tumor immune biology will build a foundation for the development of novel biomarkers and therapies to overcome resistance to checkpoint blockade.

PMID:
30842677
DOI:
10.1038/s41591-019-0382-x
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center