Back to Search
Start Over
Pan-tumor genomic biomarkers for PD-1 checkpoint blockade-based immunotherapy.
- Source :
-
Science (New York, N.Y.) [Science] 2018 Oct 12; Vol. 362 (6411). - Publication Year :
- 2018
-
Abstract
- Programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1) checkpoint blockade immunotherapy elicits durable antitumor effects in multiple cancers, yet not all patients respond. We report the evaluation of >300 patient samples across 22 tumor types from four KEYNOTE clinical trials. Tumor mutational burden (TMB) and a T cell-inflamed gene expression profile (GEP) exhibited joint predictive utility in identifying responders and nonresponders to the PD-1 antibody pembrolizumab. TMB and GEP were independently predictive of response and demonstrated low correlation, suggesting that they capture distinct features of neoantigenicity and T cell activation. Analysis of The Cancer Genome Atlas database showed TMB and GEP to have a low correlation, and analysis by joint stratification revealed biomarker-defined patterns of targetable-resistance biology. These biomarkers may have utility in clinical trial design by guiding rational selection of anti-PD-1 monotherapy and combination immunotherapy regimens.<br /> (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
- Subjects :
- Cell Cycle Checkpoints
Genetic Markers
Humans
Immunotherapy
Inflammation genetics
Mutation
T-Lymphocytes immunology
Transcriptome
Tumor Burden genetics
Antibodies, Monoclonal, Humanized therapeutic use
Antineoplastic Agents, Immunological therapeutic use
Biomarkers, Tumor genetics
Molecular Targeted Therapy methods
Neoplasms genetics
Neoplasms therapy
Programmed Cell Death 1 Receptor antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1095-9203
- Volume :
- 362
- Issue :
- 6411
- Database :
- MEDLINE
- Journal :
- Science (New York, N.Y.)
- Publication Type :
- Academic Journal
- Accession number :
- 30309915
- Full Text :
- https://doi.org/10.1126/science.aar3593