PSGL-1: A New Player in the Immune Checkpoint Landscape

Tinoco, Roberto; Otero, Dennis C.; Takahashi, Amy A.; Bradley, Linda M.

doi:10.1016/j.it.2017.02.002

Cited by 109 publications

(94 citation statements)

References 111 publications

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“…Recently, it has been highlighted the role of PSGL-1 as an immune checkpoint regulator that promotes T-cell exhaustion [55]. Specifically, in cancer environment it has been found that PSGL-1-deficiency enhanced T-cell antitumor immunity to melanoma [56]. In line with these data, for the first time, we reported a putative correlation between the expression of PD-L1 by prostate cancer cells and the presence of PSGL-1 positive intratumoral inflammatory infiltrate.…”

Section: Discussionsupporting

confidence: 81%

Programmed death ligand 1 expression in prostate cancer cells is associated with deep changes of the tumor inflammatory infiltrate composition

Scimeca

Bonfiglio

Urbano

et al. 2019

Urologic Oncology: Seminars and Original Investigations

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Section: Discussionsupporting

confidence: 81%

Programmed death ligand 1 expression in prostate cancer cells is associated with deep changes of the tumor inflammatory infiltrate composition

Scimeca

Bonfiglio

Urbano

et al. 2019

Urologic Oncology: Seminars and Original Investigations

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“…However, there are multiple reasons for enthusiasm about this discovery. First, the roles of PSGL‐1 and VISTA in regulating T cell activities and tumor immunity is gaining traction . Secondly, the pH and ionic environment being a factor that regulates immune receptor interactions is a novel and valuable concept.…”

Section: The Vista Ligand Mysterymentioning

confidence: 99%

VISTA: Coming of age as a multi-lineage immune checkpoint

ElTanbouly

Schaafsma

Noelle

et al. 2020

Clinical and Experimental Immunology

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The immune response is governed by a highly complex set of interactions among cells and mediators. T cells may be rendered dysfunctional by the presence of high levels of antigen in the absence of co-stimulation while myeloid cells may be programmed towards an immunosuppressive state that promotes cancer growth and metastasis while deterring tumor immunity. In addition, inhibitory programs driven by immune checkpoint regulators dampen anti-tumor immunity. The ideal cancer immunotherapy treatment will improve both cross-priming in the tumor microenvironment and relieve suppression by the inhibitory checkpoints. Recently, blockade of programmed cell death 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) has elicited impressive results, but not in all patients, so additional targets are under investigation. V-set immunoglobulin domain suppressor of T cell activation (VISTA) is a novel immunoregulatory receptor that is broadly expressed on cells of the myeloid and lymphoid lineages, and is frequently implicated as a poor prognostic indicator in multiple cancers. Importantly, antibody targeting of VISTA uniquely engages both innate and adaptive immunity. This, combined with the expression of VISTA and its non-redundant activities compared to other immune checkpoint regulators, qualifies VISTA to be a promising target for improving cancer immunotherapy.

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“…[13] PSGL-1 is both a key ligand for rolling adhesion and a receptor to enable intracellular signaling, inducing cytokine secretion, activation of SRC family kinase, β2-integrin, and potential activation of Phosphoinositide 3kinase (PI3K) signaling in either neutrophils or the endothelial cells they are rolling on. [14] In this paper, rolling adhesion is used as an assay to directly probe how PSGL-1 expression is affected by T2D conditions using controlled substrate P-selectin concentration. Our aim is to investigate how neutrophil rolling is affected by T2D-like pro-in ammatory conditions, such as hyperglycemia, and supraphysiological TNF-α, IL-6, and insulin concentrations, related solely to the interaction between PSGL-1 and P-selectin.…”

Section: Introductionmentioning

confidence: 99%

The Effect of Pro-Inflammatory Conditions on Neutrophil Rolling Adhesion

Taverner

Murad

Yasunaga

et al. 2019

Preprint

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Objective: Type 2 diabetes mellitus (T2D) is the result of a dysregulation of insulin concentrations and signaling, leading to an increase in both glucose concentration and proin ammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α. Previous work showed that T2D patients exhibited immune dysfunction associated with increased adhesion molecule expression on endothelial cell surfaces, accompanied by decreased neutrophil rolling velocity on the endothelial cell surface. Changes in cell rolling adhesion have direct vascular and immune complications such as atherosclerosis and decreased healing time seen in T2D patients. While previous studies focused primarily on how endothelial cells affect neutrophil rolling under T2D conditions, little is known on changes to neutrophils that affect their rolling. In this study, we aim to show how the rolling behaviour of neutrophils are affected by T2D conditions on a controlled substrate.Results: We found that neutrophils cultured in T2D-serum mimicking media showed an increase in cell rolling velocity compared to neutrophils under normal conditions. Speci cally, glucose alone is responsible for higher rolling velocity. While cytokines further increase the rolling velocity, they also reduce the cell size. It is likely that both glucose and cytokines reduce the PSGL-1 expression level on neutrophils.

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PSGL-1: A New Player in the Immune Checkpoint Landscape

Cited by 109 publications

References 111 publications

Programmed death ligand 1 expression in prostate cancer cells is associated with deep changes of the tumor inflammatory infiltrate composition

Programmed death ligand 1 expression in prostate cancer cells is associated with deep changes of the tumor inflammatory infiltrate composition

VISTA: Coming of age as a multi-lineage immune checkpoint

The Effect of Pro-Inflammatory Conditions on Neutrophil Rolling Adhesion

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