Evidence map›Paper›PMID 26997480›Full record

ArticleCell2016

Genomic and Transcriptomic Features of Response to Anti-PD-1 Therapy in Metastatic Melanoma.

Willy Hugo, Jesse M Zaretsky, Lu Sun, Chunying Song, Blanca Homet Moreno, Siwen Hu-Lieskovan, Beata Berent-Maoz, Jia Pang, Bartosz Chmielowski, Grace Cherry and 8 more

Erratum issued 4 registry-linked trialsAbstract readComment
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to 4 registered trials, which are not on this map. Cited by 2,073 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
2,073citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04273061 phase2recruitingnot on this mapstarted 2020, after this paper: background citation

Canadian Atezolizumab Precision Targeting for Immunotherapy Intervention

TypeinterventionalSponsorBritish Columbia Cancer AgencyRan2020 to 2027Enrolled200ConditionsBreast Cancer, Lung Cancer, Gastrointestinal Cancer, Genitourinary CancerArmsAtezolizumab
NCT04891055 unknown statusnot on this mapstarted 2018, after this paper: background citation

Prospective Translational Study Investigating Predictors of Outcome in Metastatic Renal Cell Carcinoma Patients Treated With Nivolumab (I-Rene Trial)

TypeobservationalSponsorFondazione IRCCS Istituto Nazionale dei Tumori, MilanoRan2018 to 2021Enrolled90ConditionsMetastatic Renal Cell Carcinoma
NCT05119829 unknown statusnot on this map

Melanoma: Genomic Profiles, Molecular Markers and Therapeutic Implications

TypeobservationalSponsorHellenic Cooperative Oncology GroupRan1998 to 2023Enrolled80ConditionsMelanoma
NCT05644457 recruitingnot on this mapstarted 2022, after this paper: background citation

Exploratory Study of Early Biomarkers Allowing Dynamic Assessment of Response to Treatment in Cancers of the Head and Neck

TypeobservationalSponsorRoyal Marsden NHS Foundation TrustRan2022 to 2026Enrolled50ConditionsHead and Neck CancerArmsCirculating tumour DNA dynamics
3 · Its place in the literature

Who cites it

2,073 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Trial
  3. Trial
  4. Article
  5. The Immune Checkpoint Inhibitors Journey: From Early Promise to Lasting Impact.Journal of immunotherapy and precision oncology · 2026
    Review
  6. Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
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  18. Review
  19. Article
  20. A meta-interaction basis for cell-cell communication in tissues.bioRxiv : the preprint server for biology · 2026
    Article

2,013 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors.

Willy HugoDivision of Dermatology, Department of Medicine, University of California, Los Angeles, CA 90095-1662, USA; David Geffen School of Medicine, University of California, Los Angeles, CA 90095-1662, USA.
Jesse M ZaretskyDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095-1662, USA; David Geffen School of Medicine, University of California, Los Angeles, CA 90095-1662, USA.
Lu SunDivision of Dermatology, Department of Medicine, University of California, Los Angeles, CA 90095-1662, USA; David Geffen School of Medicine, University of California, Los Angeles, CA 90095-1662, USA.
Chunying SongDivision of Dermatology, Department of Medicine, University of California, Los Angeles, CA 90095-1662, USA; David Geffen School of Medicine, University of California, Los Angeles, CA 90095-1662, USA.
Blanca Homet MorenoDivision of Hematology & Oncology, Department of Medicine, University of California, Los Angeles, CA 90095-1662, USA.
Siwen Hu-LieskovanDivision of Hematology & Oncology, Department of Medicine, University of California, Los Angeles, CA 90095-1662, USA.
Beata Berent-MaozDivision of Hematology & Oncology, Department of Medicine, University of California, Los Angeles, CA 90095-1662, USA.
Jia PangDivision of Hematology & Oncology, Department of Medicine, University of California, Los Angeles, CA 90095-1662, USA.
Bartosz ChmielowskiDivision of Hematology & Oncology, Department of Medicine, University of California, Los Angeles, CA 90095-1662, USA.
Grace CherryDivision of Hematology & Oncology, Department of Medicine, University of California, Los Angeles, CA 90095-1662, USA.
Elizabeth SejaDivision of Hematology & Oncology, Department of Medicine, University of California, Los Angeles, CA 90095-1662, USA.
Shirley LomeliDivision of Dermatology, Department of Medicine, University of California, Los Angeles, CA 90095-1662, USA; David Geffen School of Medicine, University of California, Los Angeles, CA 90095-1662, USA.
Xiangju KongDivision of Dermatology, Department of Medicine, University of California, Los Angeles, CA 90095-1662, USA; David Geffen School of Medicine, University of California, Los Angeles, CA 90095-1662, USA.
Mark C KelleyDepartment of Surgery, Vanderbilt-Ingram Cancer Center, Nashville, TN 37232, USA.
Jeffrey A SosmanDepartment of Medicine, Vanderbilt-Ingram Cancer Center, Nashville, TN 37232, USA.
Douglas B JohnsonDepartment of Medicine, Vanderbilt-Ingram Cancer Center, Nashville, TN 37232, USA.
Antoni RibasDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095-1662, USA; Division of Hematology & Oncology, Department of Medicine, University of California, Los Angeles, CA 90095-1662, USA; Division of Surgical Oncology, Department of Surgery, University of California, Los Angeles, CA 90095-1662, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90095-1662, USA; David Geffen School of Medicine, University of California, Los Angeles, CA 90095-1662, USA.
Roger S LoDivision of Dermatology, Department of Medicine, University of California, Los Angeles, CA 90095-1662, USA; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095-1662, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90095-1662, USA; David Geffen School of Medicine, University of California, Los Angeles, CA 90095-1662, USA. Electronic address: rlo@mednet.ucla.edu.

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
Vanderbilt Clinical Oncology Research Career Development ProgramK12CA090625 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Debra L. Friedman, Paula Jill Hurley · 2001 to 2026
$16.9M
Next Generation Cancer Immunotherapies to Defeat MelanomaR35CA197633 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ANTONI RIBAS · 2015 to 2026
$10.4M
TARGETED COMBINATORIAL TREATMENT OF BRAF MELANOMASP01CA168585 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LO, ROGER S · 2013 to 2017
$8.4M
Preventing MAPK inhibitor resistance in melanoma by targeting genomic instability and immune resistanceR01CA176111 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ROGER S LO · 2013 to 2026
$5.4M
NCATS NIH HHS UL1 TR000124NCI NIH HHS 1R01CA176111NCI NIH HHS K12 CA090625NCI NIH HHS K12CA0906525NCI NIH HHS P01 CA168585NCI NIH HHS P30 CA016042NCI NIH HHS R01 CA176111NCI NIH HHS R35 CA197633
6 · The paper itself

Abstract

PD-1 immune checkpoint blockade provides significant clinical benefits for melanoma patients. We analyzed the somatic mutanomes and transcriptomes of pretreatment melanoma biopsies to identify factors that may influence innate sensitivity or resistance to anti-PD-1 therapy. We find that overall high mutational loads associate with improved survival, and tumors from responding patients are enriched for mutations in the DNA repair gene BRCA2. Innately resistant tumors display a transcriptional signature (referred to as the IPRES, or innate anti-PD-1 resistance), indicating concurrent up-expression of genes involved in the regulation of mesenchymal transition, cell adhesion, extracellular matrix remodeling, angiogenesis, and wound healing. Notably, mitogen-activated protein kinase (MAPK)-targeted therapy (MAPK inhibitor) induces similar signatures in melanoma, suggesting that a non-genomic form of MAPK inhibitor resistance mediates cross-resistance to anti-PD-1 therapy. Validation of the IPRES in other independent tumor cohorts defines a transcriptomic subset across distinct types of advanced cancer. These findings suggest that attenuating the biological processes that underlie IPRES may improve anti-PD-1 response in melanoma and other cancer types.

Indexed as

Drug Resistance, NeoplasmAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic AgentsBRCA2 ProteinHumansMAP Kinase Signaling SystemMelanomaNeoplasm MetastasisNivolumabProgrammed Cell Death 1 ReceptorTranscriptomeAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic AgentsBRCA2 ProteinBRCA2 protein, humanNivolumabPDCD1 protein, humanpembrolizumabProgrammed Cell Death 1 Receptor

Identifiers

PMID26997480
PMCPMC4808437

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.