ArticleScience immunology2020
Resistance to PD1 blockade in the absence of metalloprotease-mediated LAG3 shedding.
Open access · greenAbstract read
In one paragraph
Article in Science immunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed, 1 pooled it
3.1field-weighted citation impact, top 6% 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.
- Immune Checkpoint Inhibitors: efficacy, safety, and biomarkers - a systematic review.Frontiers in oncology · 2026Pooled it
- Nivolumab and Relatlimab for the Treatment of Patients with Unresectable or Metastatic Mismatch Repair-Proficient Colorectal Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Effect of prior and first-line immunotherapy on baseline immune biomarkers and modulation of the tumor microenvironment in response to nivolumab and relatlimab combination therapy in patients with melanoma from RELATIVITY-020.Journal for immunotherapy of cancer · 2025Trial
- LAG3 checkpoint function and its mechanism of action in therapeutic targeting.Nature reviews. Immunology · 2026Review
- Ubiquitin-driven regulation of immune checkpoints in lung cancer: Mechanisms and therapeutic implications (Review).Experimental and therapeutic medicine · 2026Review
- Intratumoral bicarbonate functions as an adjuvant to potentiate PD-1 blockade in hepatocellular carcinoma.Oncogene · 2026Article
- Activation and lineage specific Lag3 expression dynamics in T cells.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Targeted shedding of extracellular membrane proteins by induced protease recruitment.bioRxiv : the preprint server for biology · 2026Article
- Immune landscape of melanoma: Tumor microenvironment, resistance mechanisms, and predictive biomarkers.World journal of clinical oncology · 2026Review
- Targeting T cell exhaustion in colorectal cancer: emerging roles of LAG-3, TIM-3, and TIGIT signaling in overcoming immunotherapy resistance.Cell communication and signaling : CCS · 2026Review
- Post-translational modifications of immune checkpoints: molecular mechanisms, tumor microenvironment remodeling, and therapeutic implications.Journal of biomedical science · 2026Review
- Unveiling the power of plumbagin: revitalizing exhausted T cells to combat tongue cancer.Cancer cell international · 2025Article
- Therapeutic potential of targeting LAG-3 in cancer.Journal for immunotherapy of cancer · 2025Review
- Rationale of using immune checkpoint inhibitors (ICIs) and anti-angiogenic agents in cancer treatment from a molecular perspective.Clinical and experimental medicine · 2025Review
- The tetravalent, bispecific properties of FS118, an anti-LAG-3/PD-L1 antibody, mediate LAG-3 shedding from CD4 + and CD8 + tumor-infiltrating lymphocytes.Anti-cancer drugs · 2025Article
- One Step Ahead: Preventing Tumor Adaptation to Immune Therapy.American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting · 2025Review
- Immune checkpoint inhibitors: From friend to foe.Toxicology reports · 2025Article
- LAG3 as a marker of immune activation in esophageal squamous carcinoma treated with concurrent chemoradiotherapy.Cancer immunology, immunotherapy : CII · 2025Article
- Unravelling T cell exhaustion through co-inhibitory receptors and its transformative role in cancer immunotherapy.Clinical and translational medicine · 2025Review
- Targeting Immune Checkpoint Inhibitors for Non-Small-Cell Lung Cancer: Beyond PD-1/PD-L1 Monoclonal Antibodies.Cancers · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 5 institutions in 2 countries.
Lawrence P AndrewsDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID 0000-0002-4923-142X
Ashwin SomasundaramDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID 0000-0003-3167-406X
Jessica M MoskovitzDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID 0000-0003-2360-6411
Andrea L Szymczak-WorkmanDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID 0000-0002-9776-049X
Chang LiuDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID 0000-0001-8924-1772
Anthony R CilloDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID 0000-0002-3213-3129
Huang LinDepartment of Biostatistics, University of Pittsburgh School of Public Health, Pittsburgh, PA, USA.ORCID 0000-0002-4892-7871
Daniel P NormolleDepartment of Biostatistics, University of Pittsburgh School of Public Health, Pittsburgh, PA, USA.ORCID 0000-0001-8675-5014
Kelly D MoynihanDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID 0000-0001-6200-7863
Ichiro TaniuchiRIKEN Center for Integrative Medical Sciences, Yokohama City, Kanagawa, Japan.ORCID 0000-0002-9853-9068
Darrell J IrvineDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID 0000-0002-8637-1405
John M KirkwoodCancer Immunology and Immunotherapy Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA.ORCID 0000-0002-3570-4476
Evan J LipsonDepartment of Oncology, Sidney Kimmel Comprehensive Cancer Center, and Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID 0000-0003-2976-0911
Robert L FerrisTumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA, USA.
Tullia C BrunoDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Creg J WorkmanDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.ORCID 0000-0002-9964-9509
Dario A A VignaliDepartment of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. dvignali@pitt.edu.ORCID 0000-0002-2771-5992
University of Pittsburgh · USBloomberg (United States) · USHoward Hughes Medical Institute · USMassachusetts Institute of Technology · USRIKEN Center for Integrative Medical Sciences · JP
Funding
VECTOR CORE FACILITYP30CA047904 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Jessie Nedrow · 1988 to 2026
$158.0MWILD TYPE P53-BASED ADJUVANT IMMUNOTHERAPY FOR SCCHNP50CA097190 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI CHRISTOPHER J. BAKKENIST · 2004 to 2026
$49.6MSynergies among inhibitory receptors in tolerance, cancer & antiviral immunityP01AI108545 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI E. John Wherry · 2015 to 2026
$30.8MStructure, Function and Mechanistic Analysis of LAG3R01AI144422 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Roy A Mariuzza, Dario AA Vignali · 2019 to 2026
$5.9MLymph node-targeted molecular vaccinesR01EB022433 · NIBIB · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI IRVINE, DARRELL J · 2016 to 2019
$1.4MSpecial BD LSRFortessaTMS10OD011925 · OD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BORGHESI, LISA · 2012 to 2012
$383kNCI NIH HHS P30 CA047904NCI NIH HHS P50 CA097190NIAID NIH HHS P01 AI108545NIAID NIH HHS R01 AI144422NIBIB NIH HHS R01 EB022433NIH HHS S10 OD011925
Abstract
Mechanisms of resistance to cancer immunotherapy remain poorly understood. Lymphocyte activation gene-3 (LAG3) signaling is regulated by a disintegrin and metalloprotease domain-containing protein-10 (ADAM10)- and ADAM17-mediated cell surface shedding. Here, we show that mice expressing a metalloprotease-resistant, noncleavable LAG3 mutant (LAG3
Indexed as
ADAM10 ProteinAdenocarcinomaAnimalsAntigens, CDCell Line, TumorColonic NeoplasmsDrug Resistance, NeoplasmEncephalomyelitis, Autoimmune, ExperimentalFemaleHead and Neck NeoplasmsHumansImmune Checkpoint InhibitorsImmunotherapyLymphocyte Activation Gene 3 ProteinMaleMelanoma, ExperimentalADAM10 ProteinAntigens, CDImmune Checkpoint InhibitorsLymphocyte Activation Gene 3 ProteinProgrammed Cell Death 1 Receptor
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