Evidence map›Paper›PMID 31645352›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2020

Neoadjuvant PD-1 Immune Checkpoint Blockade Reverses Functional Immunodominance among Tumor Antigen-Specific T Cells.

Jay Friedman, Ellen C Moore, Paul Zolkind, Yvette Robbins, Paul E Clavijo, Lilian Sun, Sarah Greene, Megan V Morisada, Wojciech K Mydlarz, Nicole Schmitt and 5 more

Open access · bronzeAbstract read
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed, 3 pooled it
3.5field-weighted citation impact, top 6% of its field
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

57 citing papers in PubMed, 3 syntheses or guidelines pooled it, 79 citations in OpenAlex.

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  5. Translational investigations in the HN1901 phase II window-of-opportunity study investigating the biological activity of an IDO1 (IO102) and PD-L1 (IO103) immune-modulatory peptide cancer vaccines in squamous cell carcinoma of the head and neck.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 6 institutions in 1 country.

Jay FriedmanTranslational Tumor Immunology Program, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland.
Ellen C MooreTranslational Tumor Immunology Program, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland.
Paul ZolkindDepartment of Otolaryngology-Head and Neck Surgery, Washington University in St. Louis, St. Louis, Missouri.
Yvette RobbinsTranslational Tumor Immunology Program, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland.
Paul E ClavijoTranslational Tumor Immunology Program, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland.
Lilian SunTranslational Tumor Immunology Program, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland.ORCID 0000-0002-7917-2942
Sarah GreeneTranslational Tumor Immunology Program, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland.ORCID 0000-0001-5223-3525
Megan V MorisadaTranslational Tumor Immunology Program, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland.ORCID 0000-0001-5957-7961
Wojciech K MydlarzDepartment of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland.
Nicole SchmittDepartment of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland.
James W HodgeLaboratory of Tumor Immunology and Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.ORCID 0000-0001-5282-3154
Hans SchreiberDepartment of Pathology, University of Chicago, Chicago, Illinois.
Carter Van WaesTumor Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland.
Ravindra UppaluriDepartment of Surgery/Otolaryngology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts.
Clint AllenTranslational Tumor Immunology Program, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland. clint.allen@nih.gov.
National Institute on Deafness and Other Communication Disorders · USJohns Hopkins University · USDana-Farber Brigham Cancer Center · USNational Institutes of Health · USUniversity of Illinois Chicago · USWashington University in St. Louis · US

Funding

Washington University Center for Cellular ImagingP30CA091842 · NCI · WASHINGTON UNIVERSITY · PI AIMEE S JAMES · 2001 to 2026
$128.0M
Characterization and Enhancement of Anti-Tumor Immune Responses in Head and Neck CancerZIADC000087 · NIDCD · NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS · PI ALLEN, CLINT · 2015 to 2022
$13.5M
Vaccine and Drug Combination Therapy for Human CancersZIABC010661 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI HODGE, JAMES · 2009 to 2025
$11.2M
Signal and Transcription Factor Network interactions in Head and Neck CancerZIADC000073 · NIDCD · NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS · PI VAN WAES, CARTER · 2009 to 2022
$9.1M
Mechanisms and Optimal Combinations of Cisplatin Chemotherapy for Head and Neck Squamous Cell CarcinomaZIADC000090 · NIDCD · NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS · PI SCHMITT, NICOLE · 2016 to 2020
$3.9M
Immunotherapeutic responses to neoantigens in head and neck cancerR01DE027736 · NIDCR · DANA-FARBER CANCER INST · PI UPPALURI, RAVINDRA · 2018 to 2022
$2.9M
GENOMIC INSIGHTS AND THERAPEUTIC TARGETING OF ORAL CANCER TUMOR INITIATING CELLSR01DE024403 · NIDCR · WASHINGTON UNIVERSITY · PI UPPALURI, RAVINDRA · 2014 to 2018
$1.9M
DEVELOPMENT OF INFORMATICS RESOURCES FOR INTERPRETATION OF CLINICALLY ACTIONABLE VARIANTS IN CANCERU01CA209936 · NCI · WASHINGTON UNIVERSITY · PI GRIFFITH, OBI L. · 2016 to 2018
$1.0M
Integrated Analysis & Interpretation of Whole Genome Exome & Transcriptome SequenR00HG007940 · NHGRI · WASHINGTON UNIVERSITY · PI GRIFFITH, MALACHI · 2017 to 2019
$724k
DEFINING THE REGULATORY, NON-CODING, MUTATIONAL LANDSCAPE OF BREAST CANCERK22CA188163 · NCI · WASHINGTON UNIVERSITY · PI GRIFFITH, OBI L. · 2014 to 2016
$515k
Intramural NIH HHS ZIA DC000087NCI NIH HHS K22 CA188163NCI NIH HHS P30 CA091842NCI NIH HHS U01 CA209936NHGRI NIH HHS R00 HG007940NIDCR NIH HHS R01 DE024403NIDCR NIH HHS R01 DE027736
6 · The paper itself

Abstract

purposeSurgical resection of primary tumor with regional lymphadenectomy remains the treatment of choice for patients with advanced human papillomavirus-negative head and neck squamous cell carcinoma. However, even when pathologic disease-free margins can be achieved, locoregional and/or distant disease relapse remains high. Perioperative immunotherapy may improve outcomes, but mechanistic data supporting the use of neoadjuvant or adjuvant treatment clinically are sparse. EXPERIMENTAL

designTwo syngeneic models of oral cavity carcinoma with defined T-cell antigens were treated with programmed death receptor 1 (PD-1) mAb before or after surgical resection of primary tumors, and antigen-specific T-cell responses were explored with functional and

resultsWe demonstrated that functional immunodominance developed among T cells targeting multiple independent tumor antigens. T cells specific for subdominant antigens expressed greater levels of PD-1. Neoadjuvant, but not adjuvant, PD-1 immune checkpoint blockade broke immunodominance and induced T-cell responses to dominant and subdominant antigens. Using tumors lacking the immunodominant antigen as a model of antigen escape, neoadjuvant PD-1 immune checkpoint blockade induced effector T-cell immunity against tumor cells lacking immunodominant but retaining subdominant antigen. When combined with complete surgical excision, neoadjuvant PD-1 immune checkpoint blockade led to formation of immunologic memory capable of preventing engraftment of tumors lacking the immunodominant but retaining subdominant antigen.

conclusionsTogether, these results implicate PD-1 expression by T cells in the mechanism of functional immunodominance among independent T-cell clones within a progressing tumor and support the use of neoadjuvant PD-1 immune checkpoint blockade in patients with surgically resectable carcinomas.

Indexed as

AnimalsAntibodies, MonoclonalCell Line, TumorHumansImmunodominant EpitopesImmunotherapyMiceMice, Inbred C57BLMouth NeoplasmsNeoadjuvant TherapyProgrammed Cell Death 1 ReceptorT-LymphocytesTumor MicroenvironmentXenograft Model Antitumor AssaysAntibodies, MonoclonalImmunodominant EpitopesPdcd1 protein, mouseProgrammed Cell Death 1 Receptor

Identifiers

PMID31645352
PMCPMC7002203
OpenAlexW2981322953

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Registered trials

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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.