Pulse Brain · Growing Health Evidence Index
Tier 3 — Observational / field trialPeer-reviewed

Pan-tumor genomic biomarkers for PD-1 checkpoint blockade–based immunotherapy

Răzvan Cristescu, Robin Mogg, Mark Ayers, Andrew Albright, Erin Murphy, Jennifer H. Yearley, Xinwei Sher, Xiao Qiao Liu, Hongchao Lu, Michael Nebozhyn, Chunsheng Zhang, Jared Lunceford, Andrew K. Joe, Jonathan D. Cheng, Andrea L. Webber, Nageatte Ibrahim, Elizabeth R. Plimack, Patrick A. Ott, Tanguy Y. Seiwert, Antoni Ribas, Terrill K. McClanahan, Joanne E. Tomassini, Andrey Loboda, David R. Kaufman

Science · 2018

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Summary

This exploratory analysis of data from four clinical trials of pembrolizumab, a PD-1 checkpoint inhibitor, examined over 300 patient samples across 22 tumour types to evaluate the predictive value of genomic and immunological biomarkers. Two proposed signatures—tumour mutational burden and a T cell-inflamed microenvironment—were analysed both independently and in combination to assess their utility in predicting immunotherapy response. The findings suggest that TMB and GEP capture distinct biological features and may have complementary predictive value, though the abstract does not provide detailed effect sizes or overall accuracy metrics.

UK applicability

This research is directly applicable to UK oncology practice, where pembrolizumab and other PD-1 inhibitors are standard treatments for multiple cancer types. The identification of predictive biomarkers could inform patient selection and stratification within NHS cancer services, though implementation would require validation in UK patient populations and integration with routine diagnostic pathways.

Key measures

Tumour mutational burden (TMB); T cell-inflamed gene expression profile (GEP); patient response rates to pembrolizumab; correlation between TMB and GEP

Outcomes reported

The study evaluated tumour mutational burden (TMB) and T cell-inflamed gene expression profile (GEP) as predictive biomarkers for pembrolizumab response across 300+ patient samples spanning 22 tumour types. The analysis assessed the joint and independent predictive utility of these two biomarkers in identifying responders and non-responders to PD-1 checkpoint blockade immunotherapy.

Theme
General food systems / other
Subject
Other / interdisciplinary
Study type
Research
Study design
Exploratory analysis of clinical trial data
Source type
Peer-reviewed study
Status
Published
Geography
United States
System type
Human clinical
DOI
10.1126/science.aar3593
Catalogue ID
SNmoh0dxe9-kff7k7

Topic tags

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