ArticleScience translational medicine2017
Integrated molecular analysis of tumor biopsies on sequential CTLA-4 and PD-1 blockade reveals markers of response and resistance.
Erratum issuedOpen access · greenAbstract read
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Article in Science translational medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 598 papers.
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598citing papers in PubMed
33.2field-weighted citation impact, top 1% of its field
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Who cites it
598 citing papers in PubMed, 908 citations in OpenAlex.
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- Prognostic alternative mRNA splicing signature and immune infiltration in prostate cancer.Journal of applied genetics · 2026Article
- A Targetable Developmental Program Coregulates Angiogenesis and Immune Evasion in Melanoma.Cancer discovery · 2026Article
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- Somatic copy number alterations profiling in non-small cell lung cancer and their correlation with clinical efficacy in first-line treatment.Genome medicine · 2026Article
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- TCR sequencing in cancer immunology and immunotherapy: what, when, where, why, and how.Journal for immunotherapy of cancer · 2026Review
- Identification and validation of an 11-kinase signature that predicts chemo- and radiosensitivity in gastric cancer.EBioMedicine · 2026Article
- Tumor-infiltrating lymphocytes demonstrate potent anti-tumor efficacy and synergize with PD-1 blockade in bladder cancer.Journal of translational medicine · 2026Article
- TCRcloud: a global visualization tool for T-cell and B-cell receptor transcripts.Journal of translational medicine · 2026Article
- Association of copy number alterations with the immune transcriptomic landscape in cancer.NPJ systems biology and applications · 2026Article
538 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
40 authors at 2 institutions in 2 countries.
Whijae RohDepartment of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0002-7395-9939
Pei-Ling ChenDepartment of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0002-4600-0052
Alexandre ReubenDepartment of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0003-4510-0382
Christine N SpencerDepartment of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0002-3287-0292
Peter A PrietoDepartment of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
John P MillerOncology Research for Biologics and Immunotherapy Translation, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0002-3405-2576
Vancheswaran GopalakrishnanDepartment of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0002-8704-035X
Feng WangDepartment of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Zachary A CooperDepartment of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0003-1059-0940
Sangeetha M ReddyDivision of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Curtis GumbsDepartment of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0001-8026-0897
Latasha LittleDepartment of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0001-9690-6314
Qing ChangDepartment of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Wei-Shen ChenDepartment of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0002-3637-7948
Khalida WaniDepartment of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Mariana Petaccia De MacedoDepartment of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Eveline ChenDepartment of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0001-8967-3890
Jacob L Austin-BrenemanDepartment of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0002-4841-6588
Hong JiangDepartment of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Jason RoszikDepartment of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0002-4561-6170
Michael T TetzlaffDepartment of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0001-7899-4138
Michael A DaviesDepartment of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Jeffrey E GershenwaldDepartment of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0003-4519-5369
Hussein TawbiDepartment of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0003-1942-851X
Alexander J LazarDepartment of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0002-6395-4499
Patrick HwuDepartment of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0003-0554-2856
Wen-Jen HwuDepartment of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0003-1674-0751
Adi DiabDepartment of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0002-0153-0244
Isabella C GlitzaDepartment of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0002-4530-7765
Sapna P PatelDepartment of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Scott E WoodmanDepartment of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Rodabe N AmariaDepartment of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Victor G PrietoDepartment of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.ORCID 0000-0001-9204-7161
Jianhua HuDepartment of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Padmanee SharmaDepartment of Immunology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
James P AllisonDepartment of Immunology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Lynda ChinUniversity of Texas System, Austin, TX 78701, USA.
Jianhua ZhangApplied Cancer Science Institute, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Jennifer A WargoDepartment of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. afutreal@mdanderson.org jwargo@mdanderson.org.ORCID 0000-0003-3438-7576
P Andrew FutrealDepartment of Genomic Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. afutreal@mdanderson.org jwargo@mdanderson.org.ORCID 0000-0001-8663-2671
The University of Texas MD Anderson Cancer Center · USThe University of Texas System · US
Funding
Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8MTRAINING OF ACADEMIC SURGICAL ONCOLOGISTST32CA009599 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Ashley M Holder, Jennifer A. Wargo · 1988 to 2026
$13.2MTRAINING FOR ACADEMIC ONCOLOGY/HEMATOLOGYT32CA009666 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Michael Davies, Courtney DiNardo · 1994 to 2026
$9.8MRole of Tumor Stroma in Therapeutic Response and ResistanceU54CA163125 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI FLAHERTY, KEITH T, FLAHERTY, KEITH T · 2011 to 2015
$4.4MThe role of the PI3K pathway in immune resistanceR01CA187076 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DAVIES, MICHAEL, HWU, PATRICK · 2014 to 2018
$2.0MMultidisciplinary Subspecialty Pathology Research Fellowship ProgramT32CA163185 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI CZERNIAK, BOGDAN A, KEYOMARSI, KHANDAN · 2011 to 2015
$1.7MExploring synergy of combined BRAF-targeted therapy & immunotherapy for melanomaK08CA160692 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI WARGO, JENNIFER A. · 2012 to 2016
$713kNCI NIH HHS K08 CA160692NCI NIH HHS P30 CA016672NCI NIH HHS R01 CA187076NCI NIH HHS T32 CA009599NCI NIH HHS T32 CA009666NCI NIH HHS T32 CA163185NCI NIH HHS U54 CA163125
Abstract
Immune checkpoint blockade produces clinical benefit in many patients. However, better biomarkers of response are still needed, and mechanisms of resistance remain incompletely understood. To address this, we recently studied a cohort of melanoma patients treated with sequential checkpoint blockade against cytotoxic T lymphocyte antigen-4 (CTLA-4) followed by programmed death receptor-1 (PD-1) and identified immune markers of response and resistance. Building on these studies, we performed deep molecular profiling including T cell receptor sequencing and whole-exome sequencing within the same cohort and demonstrated that a more clonal T cell repertoire was predictive of response to PD-1 but not CTLA-4 blockade. Analysis of CNAs identified a higher burden of copy number loss in nonresponders to CTLA-4 and PD-1 blockade and found that it was associated with decreased expression of genes in immune-related pathways. The effect of mutational load and burden of copy number loss on response was nonredundant, suggesting the potential utility of a combinatorial biomarker to optimize patient care with checkpoint blockade therapy.
Indexed as
Drug Resistance, NeoplasmBiomarkers, TumorBiopsyClone CellsCohort StudiesCTLA-4 AntigenDNA Copy Number VariationsGene DosageGenomeHumansMutationNeoplasmsProgrammed Cell Death 1 ReceptorT-LymphocytesBiomarkers, TumorCTLA-4 AntigenProgrammed Cell Death 1 Receptor
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