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Special Issue "PD-L1, A Master Regulator of Immunity 2.0"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: 30 September 2021.

Special Issue Editor

Dr. Grazyna Kochan
E-Mail Website
Guest Editor
Oncoimmunology Group, Biomedical Research Center of Navarre‐Navarrabiomed, Fundación Miguel Servet, IdISNA, Pamplona, Spain

Special Issue Information

Dear Colleagues,

Programmed cell death ligand (PD-L1) is a co-inhibitory molecule that is expressed on immune cells and cancer cells. Through binding with its receptor, programmed death 1 (PD-1) on the T cell surface, regulates their activity. In that way, adaptive immune responses mediated by T cells against invading pathogens are strictly regulated, thereby avoiding collateral damage to the host. However, this regulatory circuit is dysregulated in several diseases as chronic infection, transplantation immunity, autoimmunity, and cancer to dampen immune responses prematurely. Blocking the PD-1:PD-L1 immune checkpoint axis has, therefore, garnered substantial interest especially in oncology. In cancer, PD-1:PD-L1 blockade has resulted in unprecedented successes in individual patients across a variety of cancer types. However, a large number of patients fail to respond to PD-1:PD-L1 blockade. Insights into different mechanisms underlying this therapy failure are gradually being gained. These insights highlight the complexity of the immune system regulatory interaction with cancer cells. Numerous studies have begun to shed light on how combination with other therapies could enhance the response rates to PD-1:PD-L1 blockade.

Dr. Grazyna Kochan
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • PD-1
  • PD-L1
  • T cell
  • Immune checkpoint
  • Myeloid cell
  • Biomarker
  • Cancer
  • Auto-immunity
  • Infectious disease

Published Papers (5 papers)

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Research

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Open AccessArticle
PD-1 and PD-L1 Expression on Circulating Lymphocytes as a Marker of Epstein-Barr Virus Reactivation-Associated Proliferative Glomerulonephritis
Int. J. Mol. Sci. 2020, 21(21), 8001; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21218001 - 27 Oct 2020
Cited by 1 | Viewed by 543
Abstract
Alterations to the programmed cell death protein-1 (PD-1) pathway were previously shown to be involved in a poorer prognosis for patients with proliferative glomerulonephritis (PGN). Here, we investigated the association between several infectious agents and the expression of PD-1 and its ligand (PD-L1) [...] Read more.
Alterations to the programmed cell death protein-1 (PD-1) pathway were previously shown to be involved in a poorer prognosis for patients with proliferative glomerulonephritis (PGN). Here, we investigated the association between several infectious agents and the expression of PD-1 and its ligand (PD-L1) on T and B lymphocytes in patients with PGN and nonproliferative glomerulonephritis (NPGN). A cohort of 45 newly-diagnosed patients (23 with PGN and 22 with NPGN) and 20 healthy volunteers was enrolled. The percentage of peripheral blood mononuclear cells expressing PD-1 and PD-L1 antigens was determined by flow cytometry. We found PD-1 and PD-L1 expression on T and B lymphocytes was higher in PGN patients than in NPGN patients and controls. We also found that reactivation of the Epstein-Barr virus (EBV) correlated with the expression of PD-1/PD-L1 antigens in patients with PGN. Further receiver operating characteristic analysis indicated that PD-1 expression could distinguish EBV-positive PGN patients from those with NPGN or healthy controls. The use of PD-1 expression as a non-invasive marker of PGN should be further investigated. Full article
(This article belongs to the Special Issue PD-L1, A Master Regulator of Immunity 2.0)
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Review

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Open AccessReview
Role of PD-L1 in Gut Mucosa Tolerance and Chronic Inflammation
Int. J. Mol. Sci. 2020, 21(23), 9165; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21239165 - 01 Dec 2020
Viewed by 633
Abstract
The gastrointestinal (GI) mucosa is among the most complex systems in the body. It has a diverse commensal microbiome challenged continuously by food and microbial components while delivering essential nutrients and defending against pathogens. For these reasons, regulatory cells and receptors are likely [...] Read more.
The gastrointestinal (GI) mucosa is among the most complex systems in the body. It has a diverse commensal microbiome challenged continuously by food and microbial components while delivering essential nutrients and defending against pathogens. For these reasons, regulatory cells and receptors are likely to play a central role in maintaining the gut mucosal homeostasis. Recent lessons from cancer immunotherapy point out the critical role of the B7 negative co-stimulator PD-L1 in mucosal homeostasis. In this review, we summarize the current knowledge supporting the critical role of PD-L1 in gastrointestinal mucosal tolerance and how abnormalities in its expression and signaling contribute to gut inflammation and cancers. Abnormal expression of PD-L1 and/or the PD-1/PD-L1 signaling pathways have been observed in the pathology of the GI tract. We also discuss the current gap in our knowledge with regards to PD-L1 signaling in the GI tract under homeostasis and pathology. Finally, we summarize the current understanding of how this pathway is currently targeted to develop novel therapeutic approaches. Full article
(This article belongs to the Special Issue PD-L1, A Master Regulator of Immunity 2.0)
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Open AccessReview
Delicate Role of PD-L1/PD-1 Axis in Blood Vessel Inflammatory Diseases: Current Insight and Future Significance
Int. J. Mol. Sci. 2020, 21(21), 8159; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21218159 - 31 Oct 2020
Cited by 2 | Viewed by 688
Abstract
Immune checkpoint molecules are the antigen-independent generator of secondary signals that aid in maintaining the homeostasis of the immune system. The programmed death ligand-1 (PD-L1)/PD-1 axis is one among the most extensively studied immune-inhibitory checkpoint molecules, which delivers a negative signal for T [...] Read more.
Immune checkpoint molecules are the antigen-independent generator of secondary signals that aid in maintaining the homeostasis of the immune system. The programmed death ligand-1 (PD-L1)/PD-1 axis is one among the most extensively studied immune-inhibitory checkpoint molecules, which delivers a negative signal for T cell activation by binding to the PD-1 receptor. The general attributes of PD-L1’s immune-suppressive qualities and novel mechanisms on the barrier functions of vascular endothelium to regulate blood vessel-related inflammatory diseases are concisely reviewed. Though targeting the PD-1/PD-L1 axis has received immense recognition—the Nobel Prize in clinical oncology was awarded in the year 2018 for this discovery—the use of therapeutic modulating strategies for the PD-L1/PD-1 pathway in chronic inflammatory blood vessel diseases is still limited to experimental models. However, studies using clinical specimens that support the role of PD-1 and PD-L1 in patients with underlying atherosclerosis are also detailed. Of note, delicate balances in the expression levels of PD-L1 that are needed to preserve T cell immunity and to curtail acute as well as chronic infections in underlying blood vessel diseases are discussed. A significant link exists between altered lipid and glucose metabolism in different cells and the expression of PD-1/PD-L1 molecules, and its possible implications on vascular inflammation are justified. This review summarizes the most recent insights concerning the role of the PD-L1/PD-1 axis in vascular inflammation and, in addition, provides an overview exploring the novel therapeutic approaches and challenges of manipulating these immune checkpoint proteins, PD-1 and PD-L1, for suppressing blood vessel inflammation. Full article
(This article belongs to the Special Issue PD-L1, A Master Regulator of Immunity 2.0)
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Open AccessReview
Spatial and Temporal Changes in PD-L1 Expression in Cancer: The Role of Genetic Drivers, Tumor Microenvironment and Resistance to Therapy
Int. J. Mol. Sci. 2020, 21(19), 7139; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21197139 - 27 Sep 2020
Cited by 5 | Viewed by 954
Abstract
Immunotherapies blocking immune inhibitory receptors programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) on T-cells have dramatically improved patient outcomes in a range of advanced cancers. However, the lack of response, and the development of resistance remain major obstacles to long-term improvements [...] Read more.
Immunotherapies blocking immune inhibitory receptors programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) on T-cells have dramatically improved patient outcomes in a range of advanced cancers. However, the lack of response, and the development of resistance remain major obstacles to long-term improvements in patient outcomes. There is significant interest in the clinical use of biomarkers to improve patient selection, and the expression of PD-1 ligand 1 (PD-L1) is often reported as a potential biomarker of response. However, accumulating evidence suggests that the predictive value of PD-L1 expression in tumor biopsies is relatively low due, in part, to its complex biology. In this review, we discuss the biological consequences of PD-L1 expression by various cell types within the tumor microenvironment, and the complex mechanisms that regulate PD-L1 expression at the genomic, transcriptomic and proteomic levels. Full article
(This article belongs to the Special Issue PD-L1, A Master Regulator of Immunity 2.0)
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Open AccessReview
PD-L1 in Systemic Immunity: Unraveling Its Contribution to PD-1/PD-L1 Blockade Immunotherapy
Int. J. Mol. Sci. 2020, 21(16), 5918; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21165918 - 18 Aug 2020
Cited by 1 | Viewed by 815
Abstract
The use of monoclonal antibodies targeting PD-1/PD-L1 axis completely changed anticancer treatment strategies. However, despite the significant improvement in overall survival and progression-free survival of patients undergoing these immunotherapy treatments, the only clinically accepted biomarker with some prediction capabilities for the outcome of [...] Read more.
The use of monoclonal antibodies targeting PD-1/PD-L1 axis completely changed anticancer treatment strategies. However, despite the significant improvement in overall survival and progression-free survival of patients undergoing these immunotherapy treatments, the only clinically accepted biomarker with some prediction capabilities for the outcome of the treatment is PD-L1 expression in tumor biopsies. Nevertheless, even when having PD-L1-positive tumors, numerous patients do not respond to these treatments. Considering the high cost of these therapies and the risk of immune-related adverse events during therapy, it is necessary to identify additional biomarkers that would facilitate stratifying patients in potential responders and non-responders before the start of immunotherapies. Here, we review the utility of PD-L1 expression not only in tumor cells but in immune system cells and their influence on the antitumor activity of immune cell subsets. Full article
(This article belongs to the Special Issue PD-L1, A Master Regulator of Immunity 2.0)
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