Creg J. Workman
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View article: Tumor-specific stem-like progenitor exhausted CD8+ T cell subsets diverge into terminally exhausted cells and long-lived memory T cells 3102
Tumor-specific stem-like progenitor exhausted CD8+ T cell subsets diverge into terminally exhausted cells and long-lived memory T cells 3102 Open
Description Chronic T cell stimulation in tumors and chronic viral infections leads to T cell exhaustion, a state of dysfunction. As the inhibitory receptor LAG3 is expressed by all exhausted T (TEX) cells, we generated a Lag3 lineage trac…
View article: Interferon-γ derived from exhausted T cells contributes to both maintaining exhaustion within the tumor microenvironment and the memory recall response 3318
Interferon-γ derived from exhausted T cells contributes to both maintaining exhaustion within the tumor microenvironment and the memory recall response 3318 Open
Description Exhausted T cells (TEX) have traditionally been considered dysfunctional defined by impaired production of cytotoxic cytokines. However, recent studies have provided evidence that these cells may not be fully dysfunctional and …
View article: Ligand-induced ubiquitination unleashes LAG3 immune checkpoint function by hindering membrane sequestration of signaling motifs
Ligand-induced ubiquitination unleashes LAG3 immune checkpoint function by hindering membrane sequestration of signaling motifs Open
Lymphocyte activation gene 3 (LAG3) has emerged as a promising cancer immunotherapy target, but the mechanism underlying LAG3 activation upon ligand engagement remains elusive. Here, LAG3 was found to undergo robust non-K48-linked polyubiq…
View article: Regulatory T cells in the tumor microenvironment display a unique chromatin accessibility profile
Regulatory T cells in the tumor microenvironment display a unique chromatin accessibility profile Open
Regulatory T cells (Tregs) are a suppressive CD4+ T cell population that limit the antitumor immune response. In this study, we analyzed the chromatin accessibility of Tregs in the murine tumor microenvironment (TME) to identify tumor-spec…
View article: Neuronal LAG3 facilitates pathogenic α-synuclein neuron-to-neuron propagation
Neuronal LAG3 facilitates pathogenic α-synuclein neuron-to-neuron propagation Open
Lymphocyte activation gene 3 (LAG3) is a key receptor involved in the propagation of pathological proteins in Parkinson disease (PD). This study investigates the role of neuronal LAG3 in mediating the binding, uptake, and propagation of al…
View article: Ebi3 Binding to IFN-γ and IL-10 Limits Their Function
Ebi3 Binding to IFN-γ and IL-10 Limits Their Function Open
EBV-induced gene 3 (Ebi3) is a β subunit within the IL-12 cytokine family that canonically binds to α subunits p19, p28, or p35 to form the heterodimeric cytokines IL-39, IL-27, and IL-35, respectively. In the last decade, the binding part…
View article: Author Correction: Aplp1 interacts with Lag3 to facilitate transmission of pathologic α-synuclein
Author Correction: Aplp1 interacts with Lag3 to facilitate transmission of pathologic α-synuclein Open
The original version of this Article contained an error in Fig. 4, in which the statistical significance for conditions 410C9 versus Lag3 -
View article: Aplp1 interacts with Lag3 to facilitate transmission of pathologic α-synuclein
Aplp1 interacts with Lag3 to facilitate transmission of pathologic α-synuclein Open
Pathologic α-synuclein (α-syn) spreads from cell-to-cell, in part, through binding to the lymphocyte-activation gene 3 (Lag3). Here we report that amyloid β precursor-like protein 1 (Aplp1) interacts with Lag3 that facilitates the binding,…
View article: Lymphocyte‐Activation Gene 3 Facilitates Pathological Tau Neuron‐to‐Neuron Transmission (Adv. Sci. 16/2024)
Lymphocyte‐Activation Gene 3 Facilitates Pathological Tau Neuron‐to‐Neuron Transmission (Adv. Sci. 16/2024) Open
Tau preformed Fibrils The pathological tau transmission mechanism was elusive. Despite known neuronal uptake pathways, tau‐fibril‐specific receptor‐mediated uptake routes remained obscure, akin to the “maze”. In article number 2303775, Val…
View article: Lymphocyte‐Activation Gene 3 Facilitates Pathological Tau Neuron‐to‐Neuron Transmission
Lymphocyte‐Activation Gene 3 Facilitates Pathological Tau Neuron‐to‐Neuron Transmission Open
The spread of prion‐like protein aggregates is a common driver of pathogenesis in various neurodegenerative diseases, including Alzheimer's disease (AD) and related Tauopathies. Tau pathologies exhibit a clear progressive spreading pattern…
View article: Integrated BATF transcriptional network regulates suppressive intratumoral regulatory T cells
Integrated BATF transcriptional network regulates suppressive intratumoral regulatory T cells Open
Human regulatory T cells (T regs ) are crucial regulators of tissue repair, autoimmune diseases, and cancer. However, it is challenging to inhibit the suppressive function of T regs for cancer therapy without affecting immune homeostasis. …
View article: Pathological Tau transmission initiated by binding lymphocyte-activation gene 3
Pathological Tau transmission initiated by binding lymphocyte-activation gene 3 Open
The spread of prion-like protein aggregates is believed to be a common driver of pathogenesis in many neurodegenerative diseases. Accumulated tangles of filamentous Tau protein are considered pathogenic lesions of Alzheimer’s disease (AD) …
View article: Data from Systemic Immune Dysfunction in Cancer Patients Driven by IL6 Induction of LAG3 in Peripheral CD8<sup>+</sup> T Cells
Data from Systemic Immune Dysfunction in Cancer Patients Driven by IL6 Induction of LAG3 in Peripheral CD8<sup>+</sup> T Cells Open
Many cancer patients do not develop a durable response to the current standard-of-care immunotherapies, despite substantial advances in targeting immune inhibitory receptors. A potential compounding issue, which may serve as an unappreciat…
View article: Supplementary Data from Systemic Immune Dysfunction in Cancer Patients Driven by IL6 Induction of LAG3 in Peripheral CD8<sup>+</sup> T Cells
Supplementary Data from Systemic Immune Dysfunction in Cancer Patients Driven by IL6 Induction of LAG3 in Peripheral CD8<sup>+</sup> T Cells Open
Supplementary Data from Systemic Immune Dysfunction in Cancer Patients Driven by IL6 Induction of LAG3 in Peripheral CD8+ T Cells
View article: Data from Systemic Immune Dysfunction in Cancer Patients Driven by IL6 Induction of LAG3 in Peripheral CD8<sup>+</sup> T Cells
Data from Systemic Immune Dysfunction in Cancer Patients Driven by IL6 Induction of LAG3 in Peripheral CD8<sup>+</sup> T Cells Open
Many cancer patients do not develop a durable response to the current standard-of-care immunotherapies, despite substantial advances in targeting immune inhibitory receptors. A potential compounding issue, which may serve as an unappreciat…
View article: Supplementary Data from Systemic Immune Dysfunction in Cancer Patients Driven by IL6 Induction of LAG3 in Peripheral CD8<sup>+</sup> T Cells
Supplementary Data from Systemic Immune Dysfunction in Cancer Patients Driven by IL6 Induction of LAG3 in Peripheral CD8<sup>+</sup> T Cells Open
Supplementary Data from Systemic Immune Dysfunction in Cancer Patients Driven by IL6 Induction of LAG3 in Peripheral CD8+ T Cells
View article: Supplementary Tables 1-2, Figures 1-11 from Immune Inhibitory Molecules LAG-3 and PD-1 Synergistically Regulate T-cell Function to Promote Tumoral Immune Escape
Supplementary Tables 1-2, Figures 1-11 from Immune Inhibitory Molecules LAG-3 and PD-1 Synergistically Regulate T-cell Function to Promote Tumoral Immune Escape Open
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View article: Supplementary Tables 1-2, Figures 1-11 from Immune Inhibitory Molecules LAG-3 and PD-1 Synergistically Regulate T-cell Function to Promote Tumoral Immune Escape
Supplementary Tables 1-2, Figures 1-11 from Immune Inhibitory Molecules LAG-3 and PD-1 Synergistically Regulate T-cell Function to Promote Tumoral Immune Escape Open
PDF file - 1.1MB
View article: Data from Immune Inhibitory Molecules LAG-3 and PD-1 Synergistically Regulate T-cell Function to Promote Tumoral Immune Escape
Data from Immune Inhibitory Molecules LAG-3 and PD-1 Synergistically Regulate T-cell Function to Promote Tumoral Immune Escape Open
Inhibitory receptors on immune cells are pivotal regulators of immune escape in cancer. Among these inhibitory receptors, CTLA-4 (targeted clinically by ipilimumab) serves as a dominant off-switch while other receptors such as PD-1 and LAG…
View article: Data from Immune Inhibitory Molecules LAG-3 and PD-1 Synergistically Regulate T-cell Function to Promote Tumoral Immune Escape
Data from Immune Inhibitory Molecules LAG-3 and PD-1 Synergistically Regulate T-cell Function to Promote Tumoral Immune Escape Open
Inhibitory receptors on immune cells are pivotal regulators of immune escape in cancer. Among these inhibitory receptors, CTLA-4 (targeted clinically by ipilimumab) serves as a dominant off-switch while other receptors such as PD-1 and LAG…
View article: 952 The temporal contribution of interferon-γ in driving T-cell exhaustion and response to immune checkpoint blockade
952 The temporal contribution of interferon-γ in driving T-cell exhaustion and response to immune checkpoint blockade Open
Background Immune checkpoint blockade (ICB) therapies have revolutionized treatment for cancer patients, yet minority do not respond, highlighting the importance of understanding therapeutic resistance. Interferon-gamma (IFNγ) drives prote…
View article: 811 PD1 and LAG3 synergize on CD8<sup>+</sup> T cells to hinder IFNγ-dependent anti-tumor immunity
811 PD1 and LAG3 synergize on CD8<sup>+</sup> T cells to hinder IFNγ-dependent anti-tumor immunity Open
Background Overcoming immune-mediated resistance to PD1 blockade remains a challenge, however enhanced efficacy has now been demonstrated in metastatic melanoma patients with a combinatorial regimen of nivolumab and relatlimab, an anti-LAG…
View article: 1048 Interplay of IL-12 and IFNg to induce T<sub>reg</sub> fragility within the tumor microenvironment
1048 Interplay of IL-12 and IFNg to induce T<sub>reg</sub> fragility within the tumor microenvironment Open
Background Immune cells play an integral role in the prevention as well as the progression of cancers. Within the T cell compartment, regulatory T cells (Tregs) suppress the anti-tumor T cell response through use of direct and indirect mec…
View article: 1049 Reconstruction of gene regulatory networks dissects transcriptional control of intratumoral regulatory T cells
1049 Reconstruction of gene regulatory networks dissects transcriptional control of intratumoral regulatory T cells Open
Background Regulatory T cells (Treg) -targeted therapy exhibit clinical benefit and has been reported as a promising strategy. However, many gaps remain in our understanding of Treg biology within the context of tumor microenvironment (TME…
View article: Epitope Mapping of Therapeutic Antibodies Targeting Human LAG3
Epitope Mapping of Therapeutic Antibodies Targeting Human LAG3 Open
Lymphocyte activation gene 3 protein (LAG3; CD223) is an inhibitory receptor that is highly upregulated on exhausted T cells in tumors and chronic viral infection. Consequently, LAG3 is now a major immunotherapeutic target for the treatmen…