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PD-L1, a Master Regulator of Immunity in Health and Disease

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

Deadline for manuscript submissions: closed (20 April 2024) | Viewed by 7358

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Special Issue Editors

Dr. Grazyna Kochan

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Guest Editor

Oncoimmunology Group, Biomedical Research Center of Navarre‐Navarrabiomed, Fundación Miguel Servet, IdISNA, Pamplona, Spain
Interests: PD-L1; biomarker; lung cancer; immunotherapy; immune checkpoint blockade
Special Issues, Collections and Topics in MDPI journals

Dr. David Escors

E-Mail Website
Guest Editor

1. Department of Advanced Therapies, Navarrabiomed-Fundación Miguel Servet, 31008 Pamplona, Spain
2. Instituto de Investigación Sanitaria de Navarra (IdISNA), Irunlarrea 3, Navarra, 31008 Pamplona, Spain
Interests: PD-L1; PD-L1 pathway; immunotherapy; cancer; biomarkers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Programmed cell death ligand (PD-L1) is a co-inhibitory molecule that is expressed on many cell types. Through binding with its receptor, programmed death 1 (PD-1) regulates activity on the T cell surface. 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, such as chronic infection, transplantation immunity, autoimmunity, and cancers to prematurely inhibit immune responses. Blocking the PD-1–PD-L1 immune checkpoint axis has, therefore, garnered substantial interest, especially in oncology. While there is substantial literature concerning information on PD-L1 in oncological diseases, less is known about its role in autoimmune disease, or even in physiological conditions in healthy individuals. The aim of this Special Issue is to contribute to the existing knowledge on this protein in the oncological field, but also expand information on this particular target in autoimmune, infectious, and other diseases by considering its physiological conditions.

Dr. Grazyna Kochan
Dr. David Escors
Guest Editors

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 submissions that pass pre-check are 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.

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Keywords

PD-1
PD-L1
T cell
immune checkpoint
myeloid cell
biomarker
cancer
auto-immunity
infectious disease

Published Papers (4 papers)

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Editorial

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3 pages, 181 KiB

Open AccessEditorial

PD-L1, a Master Regulator of Immunity 2.0

by Grazyna Kochan

Int. J. Mol. Sci. 2023, 24(5), 4385; https://doi.org/10.3390/ijms24054385 - 23 Feb 2023

Viewed by 863

Abstract

Since the introduction of the first anticancer treatments at the beginning of the 20th century, many different chemotherapeutics have been developed [...] Full article

(This article belongs to the Special Issue PD-L1, a Master Regulator of Immunity in Health and Disease)

Review

Jump to: Editorial

23 pages, 1342 KiB

Open AccessReview

Programmed Death Ligand 1 Regulatory Crosstalk with Ubiquitination and Deubiquitination: Implications in Cancer Immunotherapy

by Soon-Bin Kim, Soonjae Hwang, Ji-Young Cha and Ho-Jae Lee

Int. J. Mol. Sci. 2024, 25(5), 2939; https://doi.org/10.3390/ijms25052939 - 03 Mar 2024

Viewed by 797

Abstract

Programmed death ligand 1 (PD-L1) plays a pivotal role in cancer immune evasion and is a critical target for cancer immunotherapy. This review focuses on the regulation of PD-L1 through the dynamic processes of ubiquitination and deubiquitination, which are crucial for its stability and function. Here, we explored the intricate mechanisms involving various E3 ubiquitin ligases and deubiquitinating enzymes (DUBs) that modulate PD-L1 expression in cancer cells. Specific ligases are discussed in detail, highlighting their roles in tagging PD-L1 for degradation. Furthermore, we discuss the actions of DUBs that stabilize PD-L1 by removing ubiquitin chains. The interplay of these enzymes not only dictates PD-L1 levels but also influences cancer progression and patient response to immunotherapies. Furthermore, we discuss the therapeutic implications of targeting these regulatory pathways and propose novel strategies to enhance the efficacy of PD-L1/PD-1-based therapies. Our review underscores the complexity of PD-L1 regulation and its significant impact on the tumor microenvironment and immunotherapy outcomes. Full article

(This article belongs to the Special Issue PD-L1, a Master Regulator of Immunity in Health and Disease)

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20 pages, 781 KiB

Open AccessReview

Molecular Farming of Pembrolizumab and Nivolumab

by Michael C. Stark, Anna M. Joubert and Michelle H. Visagie

Int. J. Mol. Sci. 2023, 24(12), 10045; https://doi.org/10.3390/ijms241210045 - 12 Jun 2023

Cited by 2 | Viewed by 2962

Abstract

Immune checkpoint inhibitors (ICIs) are a class of immunotherapy agents capable of alleviating the immunosuppressive effects exerted by tumorigenic cells. The programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) immune checkpoint is one of the most ubiquitous checkpoints utilized by tumorigenic cells for immune evasion by inducing apoptosis and inhibiting the proliferation and cytokine production of T lymphocytes. Currently, the most frequently used ICIs targeting the PD-1/PD-L1 checkpoint include monoclonal antibodies (mAbs) pembrolizumab and nivolumab that bind to PD-1 on T lymphocytes and inhibit interaction with PD-L1 on tumorigenic cells. However, pembrolizumab and nivolumab are costly, and thus their accessibility is limited in low- and middle-income countries (LMICs). Therefore, it is essential to develop novel biomanufacturing platforms capable of reducing the cost of these two therapies. Molecular farming is one such platform utilizing plants for mAb production, and it has been demonstrated to be a rapid, low-cost, and scalable platform that can be potentially implemented in LMICs to diminish the exorbitant prices, ultimately leading to a significant reduction in cancer-related mortalities within these countries. Full article

(This article belongs to the Special Issue PD-L1, a Master Regulator of Immunity in Health and Disease)

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Figure 1

13 pages, 940 KiB

Open AccessReview

Regulation of PD-L1 Expression by Nuclear Receptors

by Yoshimitsu Kiriyama and Hiromi Nochi

Int. J. Mol. Sci. 2023, 24(12), 9891; https://doi.org/10.3390/ijms24129891 - 08 Jun 2023

Cited by 2 | Viewed by 2141

Abstract

The suppression of excessive immune responses is necessary to prevent injury to the body, but it also allows cancer cells to escape immune responses and proliferate. Programmed cell death 1 (PD-1) is a co-inhibitory molecule that is present on T cells and is the receptor for programmed cell death ligand 1 (PD-L1). The binding of PD-1 to PD-L1 leads to the inhibition of the T cell receptor signaling cascade. PD-L1 has been found to be expressed in many types of cancers, such as lung, ovarian, and breast cancer, as well as glioblastoma. Furthermore, PD-L1 mRNA is widely expressed in normal peripheral tissues including the heart, skeletal muscle, placenta, lungs, thymus, spleen, kidney, and liver. The expression of PD-L1 is upregulated by proinflammatory cytokines and growth factors via a number of transcription factors. In addition, various nuclear receptors, such as androgen receptor, estrogen receptor, peroxisome-proliferator-activated receptor γ, and retinoic-acid-related orphan receptor γ, also regulate the expression of PD-L1. This review will focus on the current knowledge of the regulation of PD-L1 expression by nuclear receptors. Full article

(This article belongs to the Special Issue PD-L1, a Master Regulator of Immunity in Health and Disease)

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