ArticleNature medicine2019
A single dose of neoadjuvant PD-1 blockade predicts clinical outcomes in resectable melanoma.
4 registry-linked trialsAbstract readClinical Trial, Phase I
In one paragraph
Article in Nature medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 4 registered trials, which are not on this map. Cited by 421 papers, 4 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
421citing papers in PubMed, 4 pooled it
38.4field-weighted citation impact, top 1% of its field
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.
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.
A Phase Ib Tissue Collection Study of Pembrolizumab (MK-3475) in Subjects With Resectable Advanced Melanoma
NCT04013854 phase2active not recruitingnot on this mapstarted 2020, after this paper: background citation
Adjuvant Nivolumab or Ipilimumab + Nivolumab Determined By Pathological Response To A Single Dose Of Neoadjvuant Nivolumab
Phase II Study of Neoadjuvant Ipilimumab/Nivolumab for Patients With Recurrent, High Risk, Resectable Melanoma
NCT07277322 phase1 / phase2recruitingnot on this mapstarted 2026, after this paper: background citation
Master Protocol for A Phase 1b/2 Study of Neoadjuvant Immunotherapy in Microsatellite Stable (MSS) Colorectal Cancer (CRC) Subjects With Resectable Liver Metastases
Who cites it
421 citing papers in PubMed, 4 syntheses or guidelines pooled it, 691 citations in OpenAlex.
- Pooled it
- Anti-PD-1 and anti-PD-L1 antibodies for glioma.The Cochrane database of systematic reviews · 2025Pooled it
- Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of melanoma, version 3.0.Journal for immunotherapy of cancer · 2023Guideline
- The impact of cytoreductive nephrectomy on survival outcomes in patients with metastatic renal cell carcinoma receiving immunotherapy: An evidence-based analysis of comparative outcomes.Frontiers in immunology · 2023Pooled it
- Neoadjuvant ipilimumab plus nivolumab in melanoma: 5-year survival and biomarker analysis from the phase 2 PRADO-trial.Nature medicine · 2026Trial
- Neoadjuvant PD-1 blockade in surgically resectable desmoplastic melanoma: cohort A of the phase 2 SWOG S1512 trial.Nature cancer · 2026Trial
- Tumor and Immune Dynamics Following Sequential CDK4/6 and PD-1 Inhibition: Results from a Phase 2 Study in Dedifferentiated Liposarcoma.Cancer research communications · 2026Trial
- Lenvatinib plus transarterial chemoembolization and PD-1 inhibitors as conversion therapies for unresectable intermediate-advanced hepatocellular carcinoma: a phase 2 trial and exploratory biomolecular study.Signal transduction and targeted therapy · 2026Trial
- Neoadjuvant immune checkpoint blockade before chemoradiation for cervical squamous carcinoma (GINECO window-of-opportunity COLIBRI study): a phase II trial.Nature communications · 2026Trial
- Neoadjuvant tislelizumab with afatinib for locally advanced head and neck squamous cell carcinoma (neoCHANCE-1): a phase 2 clinical trial.Nature communications · 2025Trial
- Dual Immune Checkpoint Inhibition Plus Neoadjuvant Chemoradiotherapy in Rectal Cancer: A Randomized Clinical Trial.JAMA network open · 2025Trial
- TEIPP-vaccination in checkpoint-resistant non-small cell lung cancer: a first-in-human phase I/II dose-escalation study.Nature communications · 2025Trial
- Neo-adjuvant pembrolizumab in stage IV high-grade serous ovarian cancer: the phase II Neo-Pembro trial.Nature communications · 2025Trial
- Neoadjuvant cabozantinib for locally advanced nonmetastatic clear cell renal cell carcinoma: a phase 2 trial.Nature cancer · 2025Trial
- Neoadjuvant vidutolimod and nivolumab in high-risk resectable melanoma: A prospective phase II trial.Cancer cell · 2024Trial
- Neoadjuvant pembrolizumab, dabrafenib and trametinib in BRAFNature medicine · 2024Trial
- Combined JAK inhibition and PD-1 immunotherapy for non-small cell lung cancer patients.Science (New York, N.Y.) · 2024Trial
- Comprehensive multi-omics analysis of resectable locally advanced gastric cancer: Assessing response to neoadjuvant camrelizumab and chemotherapy in a single-center, open-label, single-arm phase II trial.Clinical and translational medicine · 2024Trial
- Nivolumab for mismatch-repair-deficient or hypermutated gynecologic cancers: a phase 2 trial with biomarker analyses.Nature medicine · 2024Trial
- Neoadjuvant atezolizumab plus chemotherapy in gastric and gastroesophageal junction adenocarcinoma: the phase 2 PANDA trial.Nature medicine · 2024Trial
361 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
37 authors at 7 institutions in 3 countries.
Alexander C HuangDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. alexander.huang@uphs.upenn.edu.ORCID http://orcid.org/0000-0002-0099-0492
Robert J OrlowskiDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Xiaowei XuAbramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Rosemarie MickParker Institute for Cancer Immunotherapy at University of Pennsylvania, Philadelphia, PA, USA.
Sangeeth M GeorgeDepartment of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Patrick K YanInstitute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-6124-1615
Sasikanth ManneInstitute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Adam A KrayaDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Bradley WubbenhorstDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Liza DorfmanDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Kurt D'AndreaDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Brandon M WenzDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Shujing LiuAbramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Lakshmi ChilukuriInstitute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Andrew KozlovAbramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Mary CarberryDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Lydia GilesDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Melanie W KierDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Felix QuagliarelloInstitute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Suzanne McGettiganDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Kristin KreiderDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Lakshmanan AnnamalaiMerck Research Laboratories, Kenilworth, NJ, USA.
Qing ZhaoMerck Research Laboratories, Kenilworth, NJ, USA.
Robin MoggMerck Research Laboratories, Kenilworth, NJ, USA.
Wei XuDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Wendy M BlumenscheinMerck Research Laboratories, Kenilworth, NJ, USA.
Jennifer H YearleyMerck Research Laboratories, Kenilworth, NJ, USA.
Gerald P LinetteDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Ravi K AmaravadiDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Lynn M SchuchterDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Ramin S HeratiDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Bertram BengschInstitute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Katherine L NathansonDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Michael D FarwellAbramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Giorgos C KarakousisAbramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
E John WherryInstitute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. wherry@pennmedicine.upenn.edu.ORCID http://orcid.org/0000-0003-0477-1956
Tara C MitchellDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. tara.mitchell@uphs.upenn.edu.ORCID http://orcid.org/0000-0002-8186-7284
University of Pennsylvania · USMerck & Co., Inc., Rahway, NJ, USA (United States) · USParker Institute for Cancer Immunotherapy · USTranslational Therapeutics (United States) · USBristol-Myers Squibb (United States) · USStemcell Technologies · CAUniversity Medical Center Freiburg · DE
Funding
UNIVERSITY OF PENNSYLVANIA CAN CTR SUPPORT GRANTP30CA016520 · NCI · UNIVERSITY OF PENNSYLVANIA · PI SHELLEY L BERGER · 1985 to 2026
$222.3MVirology CoreU19AI082630 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI Michela Locci · 2009 to 2026
$48.1MTargeting the MAP and PI3 Kinase Pathways in MelanomaP01CA114046 · NCI · WISTAR INSTITUTE · PI MURPHY, MAUREEN E. · 2008 to 2023
$37.1MSynergies among inhibitory receptors in tolerance, cancer & antiviral immunityP01AI108545 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI E. John Wherry · 2015 to 2026
$30.8MSequencing and Viral Evolution CoreU19AI117950 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI WHERRY, E. JOHN · 2015 to 2019
$12.0MRadiation and checkpoint blockade for cancer immune therapyP01CA210944 · NCI · UNIVERSITY OF PENNSYLVANIA · PI VONDERHEIDE, ROBERT H · 2017 to 2022
$11.5MTargeted Combination Therapy for MelanomaP50CA174523 · NCI · WISTAR INSTITUTE · PI HERLYN, MEENHARD F · 2014 to 2018
$11.1MCANCER RESEARCH TRAINING PROGRAMT32CA009615 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Gregory L Beatty, MICHAEL D HOGARTY · 1988 to 2026
$10.4MPostdoctoral Training Program in Genomic MedicineT32HG009495 · NHGRI · UNIVERSITY OF PENNSYLVANIA · PI Katherine L. Nathanson, Bogdan Pasaniuc · 2017 to 2026
$4.2MCellular and transcriptional control of exhausted CD8 T cells lineage dynamicsR01AI105343 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI WHERRY, E. JOHN · 2014 to 2017
$1.6MEffects of aging on the T follicular helper response to influenza vaccineK08AI114852 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI HERATI, RAMIN · 2015 to 2019
$947kNCI NIH HHS P01 CA114046NCI NIH HHS P01 CA210944NCI NIH HHS P30 CA016520NCI NIH HHS P50 CA174523NCI NIH HHS T32 CA009615NHGRI NIH HHS T32 HG009495NIAID NIH HHS K08 AI114852NIAID NIH HHS P01 AI108545NIAID NIH HHS R01 AI105343NIAID NIH HHS U19 AI082630NIAID NIH HHS U19 AI117950
Abstract
Immunologic responses to anti-PD-1 therapy in melanoma patients occur rapidly with pharmacodynamic T cell responses detectable in blood by 3 weeks. It is unclear, however, whether these early blood-based observations translate to the tumor microenvironment. We conducted a study of neoadjuvant/adjuvant anti-PD-1 therapy in stage III/IV melanoma. We hypothesized that immune reinvigoration in the tumor would be detectable at 3 weeks and that this response would correlate with disease-free survival. We identified a rapid and potent anti-tumor response, with 8 of 27 patients experiencing a complete or major pathological response after a single dose of anti-PD-1, all of whom remain disease free. These rapid pathologic and clinical responses were associated with accumulation of exhausted CD8 T cells in the tumor at 3 weeks, with reinvigoration in the blood observed as early as 1 week. Transcriptional analysis demonstrated a pretreatment immune signature (neoadjuvant response signature) that was associated with clinical benefit. In contrast, patients with disease recurrence displayed mechanisms of resistance including immune suppression, mutational escape, and/or tumor evolution. Neoadjuvant anti-PD-1 treatment is effective in high-risk resectable stage III/IV melanoma. Pathological response and immunological analyses after a single neoadjuvant dose can be used to predict clinical outcome and to dissect underlying mechanisms in checkpoint blockade.
Indexed as
Dermatologic Surgical ProceduresAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalCD8-Positive T-LymphocytesChemotherapy, AdjuvantFemaleGene Expression ProfilingHumansKaplan-Meier EstimateMaleMelanomaMiddle AgedNeoadjuvant TherapyAntibodies, Monoclonal, HumanizedAntineoplastic Agents, Immunologicalpembrolizumab
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Registered trials
NCT02434354ClinicalTrials.gov
NCT04013854ClinicalTrials.gov
NCT06365619ClinicalTrials.gov
NCT07277322ClinicalTrials.gov
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.