{"entity":{"id":"paper-cristescu-science","kind":"paper","name":"Pan-tumor genomic biomarkers for PD-1 checkpoint blockade-based immunotherapy","aka":[],"tldr":"Paper cited by one bottleneck page, indexed on Europe PMC as PubMed record 30309915 and published in Science; the citing page links this DOI, which is how the record was matched.","summary":"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.\n\nIndexed on Europe PMC as PubMed record 30309915 (DOI 10.1126/science.aar3593). Matched by DOI alone: one bottleneck page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Science 2018","url":"https://doi.org/10.1126/science.aar3593"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30309915/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/30309915"}],"tags":["europepmc-ingest"],"related":["b-immunotherapy-response"],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["science"],"dependsOn":[],"notes":[],"journal":"Science","year":2018,"doi":"10.1126/science.aar3593","pmid":"30309915","authors":"Cristescu R, Mogg R, Ayers M, et al.","paperType":"observational","findings":[],"whatItMeans":"One bottleneck page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.","caveats":["Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper."]},"route":"/key-papers/paper-cristescu-science/","neighbours":{"bottleneck":[{"id":"b-immunotherapy-response","kind":"bottleneck","name":"No one can predict who responds to immunotherapy","route":"/bottlenecks/b-immunotherapy-response/"}],"journal":[{"id":"science","kind":"journal","name":"Science","route":"/journals/science/"}]}}