LAG-3: from molecular functions to clinical applications

A LAG-3–Specific Agonist Antibody for the Treatment of T Cell–Induced Autoimmune Diseases

(2020) Mathieu Angin et al.   JOURNAL OF IMMUNOLOGY

Small Molecule Inhibition of GSK-3 Specifically Inhibits the Transcription of Inhibitory Co-receptor LAG-3 for Enhanced Anti-tumor Immunity

(2020) Christopher E. Rudd et al.   Cell Reports

FS118, a Bispecific Antibody Targeting LAG-3 and PD-L1, Enhances T-Cell Activation Resulting in Potent Antitumor Activity

(2020) Matthew Kraman et al.   CLINICAL CANCER RESEARCH

NR4A transcription factors limit CAR T cell function in solid tumours

(2019) Joyce Chen et al.   NATURE

Genome-wide analysis identifies NR4A1 as a key mediator of T cell dysfunction

(2019) Xindong Liu et al.   NATURE

Cutting Edge: IL-27 Attenuates Autoimmune Neuroinflammation via Regulatory T Cell/Lag3–Dependent but IL-10–Independent Mechanisms In Vivo

(2019) Dongkyun Kim et al.   JOURNAL OF IMMUNOLOGY

Atypical motifs in the cytoplasmic region of the inhibitory immune co-receptor LAG-3 inhibit T cell activation

(2019) Takeo K. Maeda et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Adverse effects of immune-checkpoint inhibitors: epidemiology, management and surveillance

(2019) Filipe Martins et al.   Nature Reviews Clinical Oncology

TOX is a critical regulator of tumour-specific T cell differentiation

(2019) Andrew C. Scott et al.   NATURE

TOX transcriptionally and epigenetically programs CD8+ T cell exhaustion

(2019) Omar Khan et al.   NATURE

TOX and TOX2 transcription factors cooperate with NR4A transcription factors to impose CD8+ T cell exhaustion

(2019) Hyungseok Seo et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

CD4+ T cell exhaustion revealed by high PD-1 and LAG-3 expression and the loss of helper T cell function in chronic hepatitis B

(2019) Yuejiao Dong et al.   BMC IMMUNOLOGY

Inhibitory receptors and ligands beyond PD-1, PD-L1 and CTLA-4: breakthroughs or backups

(2019) Lawrence P. Andrews et al.   NATURE IMMUNOLOGY

Double negative T cells mediate Lag3-dependent antigen-specific protection in allergic asthma

(2019) Dan Tian et al.   Nature Communications

Dual PD1/LAG3 immune checkpoint blockade limits tumor development in a murine model of chronic lymphocytic leukemia

(2018) Marina Wierz et al.   BLOOD

Regulation and Function of the PD-L1 Checkpoint

(2018) Chong Sun et al.   IMMUNITY

LAG-3 Inhibitory Receptor Expression Identifies Immunosuppressive Natural Regulatory Plasma Cells

(2018) Andreia C. Lino et al.   IMMUNITY

Immune-Related Adverse Events Associated with Immune Checkpoint Blockade

(2018) Michael A. Postow et al.   NEW ENGLAND JOURNAL OF MEDICINE

Cancer immunotherapy using checkpoint blockade

(2018) Antoni Ribas et al.   SCIENCE

Abstract 4547: Characterization of the LAG-3 targeting antibody BI 754111 in monotherapy and in combination with the anti-PD-1 antibody BI 754091

(2018) Markus Zettl et al.   CANCER RESEARCH

Abstract 3819: INCAGN02385 is an antagonist antibody targeting the co-inhibitory receptor LAG-3 for the treatment of human malignancies

(2018) David Savitsky et al.   CANCER RESEARCH

Phase I/II study of LAG525 ± spartalizumab (PDR001) in patients (pts) with advanced malignancies.

(2018) David S. Hong et al.   JOURNAL OF CLINICAL ONCOLOGY

Fibrinogen-like Protein 1 Is a Major Immune Inhibitory Ligand of LAG-3

(2018) Jun Wang et al.   CELL

LAG-3 inhibits the activation of CD4+ T cells that recognize stable pMHCII through its conformation-dependent recognition of pMHCII

(2018) Takumi Maruhashi et al.   NATURE IMMUNOLOGY

Blockade of LAG-3 Immune Checkpoint Combined With Therapeutic Vaccination Restore the Function of Tissue-Resident Anti-viral CD8+ T Cells and Protect Against Recurrent Ocular Herpes Simplex Infection and Disease

(2018) Soumyabrata Roy et al.   Frontiers in Immunology

Ablation of Transcription Factor IRF4 Promotes Transplant Acceptance by Driving Allogenic CD4 + T Cell Dysfunction

(2017) Jie Wu et al.   IMMUNITY

Transcription Factor IRF4 Promotes CD8 + T Cell Exhaustion and Limits the Development of Memory-like T Cells during Chronic Infection

(2017) Kevin Man et al.   IMMUNITY

Regulation of immune and neural function via leukocyte Ig-like receptors

(2017) Kazuya Takeda et al.   JOURNAL OF BIOCHEMISTRY

LAG-3 Protein Expression in Non–Small Cell Lung Cancer and Its Relationship with PD-1/PD-L1 and Tumor-Infiltrating Lymphocytes

(2017) Yayi He et al.   Journal of Thoracic Oncology

The role of semaphorins in immune responses and autoimmune rheumatic diseases

(2017) Masayuki Nishide et al.   Nature Reviews Rheumatology

Expression of LAG-3 defines exhaustion of intratumoral PD-1+ T cells and correlates with poor outcome in follicular lymphoma

(2017) Zhi-Zhang Yang et al.   Oncotarget

Galectin 3 as a guardian of the tumor microenvironment

(2016) Peter P. Ruvolo   BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH

Abstract 3217: MGD013, a bispecific PD-1 x LAG-3 Dual-Affinity Re-Targeting (DART®) protein with T-cell immunomodulatory activity for cancer treatment

(2016) Ross LaMotte-Mohs et al.   CANCER RESEARCH

LAG-3 Confers a Competitive Disadvantage upon Antiviral CD8+T Cell Responses

(2016) Kevin D. Cook et al.   JOURNAL OF IMMUNOLOGY

Multiple Inhibitory Pathways Contribute to Lung CD8+T Cell Impairment and Protect against Immunopathology during Acute Viral Respiratory Infection

(2016) John J. Erickson et al.   JOURNAL OF IMMUNOLOGY

Pathological  -synuclein transmission initiated by binding lymphocyte-activation gene 3

(2016) X. Mao et al.   SCIENCE

Gut environment-induced intraepithelial autoreactive CD4+ T cells suppress central nervous system autoimmunity via LAG-3

(2016) Atsushi Kadowaki et al.   Nature Communications

LAG-3 confers poor prognosis and its blockade reshapes antitumor response in head and neck squamous cell carcinoma

(2016) Wei-Wei Deng et al.   OncoImmunology

LAG3 Expression in Active Mycobacterium tuberculosis Infections

(2015) Bonnie L. Phillips et al.   AMERICAN JOURNAL OF PATHOLOGY

Orchestration and Prognostic Significance of Immune Checkpoints in the Microenvironment of Primary and Metastatic Renal Cell Cancer

(2015) N. A. Giraldo et al.   CLINICAL CANCER RESEARCH

Vaccination with LAG-3Ig (IMP321) and Peptides Induces Specific CD4 and CD8 T-Cell Responses in Metastatic Melanoma Patients--Report of a Phase I/IIa Clinical Trial

(2015) A. Legat et al.   CLINICAL CANCER RESEARCH

The Transcription Factor NFAT Promotes Exhaustion of Activated CD8 + T Cells

(2015) Gustavo J. Martinez et al.   IMMUNITY

Lymphocyte activation gene 3 negatively regulates the function of intrahepatic hepatitis C virus-specific CD8+T cells

(2015) Na Chen et al.   JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY

The Upregulation of LAG-3 on T Cells Defines a Subpopulation with Functional Exhaustion and Correlates with Disease Progression in HIV-Infected Subjects

(2015) Xiaoling Tian et al.   JOURNAL OF IMMUNOLOGY

TGF-β3-expressing CD4+CD25−LAG3+ regulatory T cells control humoral immune responses

(2015) Tomohisa Okamura et al.   Nature Communications

LAG3 and PD1 co-inhibitory molecules collaborate to limit CD8+ T cell signaling and dampen antitumor immunity in a murine ovarian cancer model

(2015) Ruea-Yea Huang et al.   Oncotarget

Galectin-3 Shapes Antitumor Immune Responses by Suppressing CD8+ T Cells via LAG-3 and Inhibiting Expansion of Plasmacytoid Dendritic Cells

(2015) T. Kouo et al.   Cancer Immunology Research

Progression of Lung Cancer Is Associated with Increased Dysfunction of T Cells Defined by Coexpression of Multiple Inhibitory Receptors

(2015) D. S. Thommen et al.   Cancer Immunology Research

LSECtin Expressed on Melanoma Cells Promotes Tumor Progression by Inhibiting Antitumor T-cell Responses

(2014) F. Xu et al.   CANCER RESEARCH

Trafficking of LAG-3 to the Surface on Activated T Cells via Its Cytoplasmic Domain and Protein Kinase C Signaling

(2014) Joonbeom Bae et al.   JOURNAL OF IMMUNOLOGY

MART-1 peptide vaccination plus IMP321 (LAG-3Ig fusion protein) in patients receiving autologous PBMCs after lymphodepletion: results of a Phase I trial

(2014) Emanuela Romano et al.   Journal of Translational Medicine

The effect of immune microenvironment on the progression and prognosis of colorectal cancer

(2014) Jinxiang Chen et al.   MEDICAL ONCOLOGY

Role of Lymphocyte Activation Gene-3 (Lag-3) in Conventional and Regulatory T Cell Function in Allogeneic Transplantation

(2014) Emanuela I. Sega et al.   PLoS One

Lymphocyte Activation Gene-3 (LAG-3) Negatively Regulates Environmentally-Induced Autoimmunity

(2014) Vibha Jha et al.   PLoS One

Lymphocyte Activation Gene 3 (LAG-3) Modulates the Ability of CD4 T-cells to Be Suppressed In Vivo

(2014) Nicholas M. Durham et al.   PLoS One

Expression regulation of co-inhibitory molecules on human natural killer cells in response to cytokine stimulations

(2013) Haoyu Sun et al.   CYTOKINE

Restoring Immune Function of Tumor-Specific CD4+ T Cells during Recurrence of Melanoma

(2013) S. R. Goding et al.   JOURNAL OF IMMUNOLOGY

A rheostat for immune responses: the unique properties of PD-1 and their advantages for clinical application

(2013) Taku Okazaki et al.   NATURE IMMUNOLOGY

Coexpression of CD49b and LAG-3 identifies human and mouse T regulatory type 1 cells

(2013) Nicola Gagliani et al.   NATURE MEDICINE

Expression of LAG-3 is coincident with the impaired effector function of HBV-specific CD8+ T cell in HCC patients

(2012) Fu-Jun Li et al.   IMMUNOLOGY LETTERS

A phase I study of IMP321 and gemcitabine as the front-line therapy in patients with advanced pancreatic adenocarcinoma

(2012) Andrea Wang-Gillam et al.   INVESTIGATIONAL NEW DRUGS

Immune Inhibitory Molecules LAG-3 and PD-1 Synergistically Regulate T-cell Function to Promote Tumoral Immune Escape

(2011) S.-R. Woo et al.   CANCER RESEARCH

Antibody-mediated depletion of lymphocyte-activation gene-3 (LAG-3+)-activated T lymphocytes prevents delayed-type hypersensitivity in non-human primates

(2011) N. Poirier et al.   CLINICAL AND EXPERIMENTAL IMMUNOLOGY

PD-1 and LAG-3 inhibitory co-receptors act synergistically to prevent autoimmunity in mice

(2011) Taku Okazaki et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Cutting Edge: Accelerated Autoimmune Diabetes in the Absence of LAG-3

(2011) M. Bettini et al.   JOURNAL OF IMMUNOLOGY

Transcription factor T-bet represses expression of the inhibitory receptor PD-1 and sustains virus-specific CD8+ T cell responses during chronic infection

(2011) Charlly Kao et al.   NATURE IMMUNOLOGY

Therapeutic blockade of PD-L1 and LAG-3 rapidly clears established blood-stage Plasmodium infection

(2011) Noah S Butler et al.   NATURE IMMUNOLOGY

LAG-3 Expression Defines a Subset of CD4+CD25highFoxp3+ Regulatory T Cells That Are Expanded at Tumor Sites

(2010) C. Camisaschi et al.   JOURNAL OF IMMUNOLOGY

First-line chemoimmunotherapy in metastatic breast carcinoma: combination of paclitaxel and IMP321 (LAG-3Ig) enhances immune responses and antitumor activity

(2010) Chrystelle Brignone et al.   Journal of Translational Medicine

Tumor-infiltrating NY-ESO-1–specific CD8+T cells are negatively regulated by LAG-3 and PD-1 in human ovarian cancer

(2010) Junko Matsuzaki et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

A Role for the Transcriptional Repressor Blimp-1 in CD8+ T Cell Exhaustion during Chronic Viral Infection

(2009) Haina Shin et al.   IMMUNITY

On the role of the inhibitory receptor LAG-3 in acute and chronic LCMV infection

(2009) Kirsten Richter et al.   INTERNATIONAL IMMUNOLOGY

LAG-3 Regulates Plasmacytoid Dendritic Cell Homeostasis

(2009) C. J. Workman et al.   JOURNAL OF IMMUNOLOGY

CD4+CD25-LAG3+ regulatory T cells controlled by the transcription factor Egr-2

(2009) T. Okamura et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection

(2008) Shawn D Blackburn et al.   NATURE IMMUNOLOGY