Targeting the PD-1/PD-L1 Signaling Pathway for Cancer Therapy: Focus on Biomarkers

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1235 - 1235

Published: Jan. 31, 2025

The PD1/PD-L1 axis plays an important immunosuppressive role during the T-cell-mediated immune response, which is essential for physiological homeostasis of system. biology immunological microenvironment extremely complex and crucial development treatment strategies immunotherapy. Characterization immunological, genomic or transcriptomic landscape cancer patients could allow discrimination between responders non-responders to anti-PD-1/PD-L1 therapy. Immune checkpoint inhibitor (ICI) therapy has shown remarkable efficacy in a variety malignancies landmark trials fundamentally changed Current research focuses on maximize patient selection therapy, clarify mechanisms resistance, improve existing biomarkers, including PD-L1 expression tumor mutational burden (TMB), discover new biomarkers. In this review, we focus function PD-1/PD-L1 signaling pathway discuss genomic, epigenetic receiving Finally, provide overview clinical testing antibodies against PD-1/PD-L1.

Language: Английский

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The emerging and challenging role of PD-L1 in patients with gynecological cancers: An updating review with clinico-pathological considerations

Gynecologic Oncology, Journal Year: 2024, Volume and Issue: 184, P. 57 - 66

Published: Jan. 30, 2024

Over recent years, there has been significant progress in the development of immunotherapeutic molecules designed to block PD-1/PD-L1 axis. These have demonstrated their ability enhance immune response by prompting T cells identify and suppress neoplastic cells. PD-L1 is a type 1 transmembrane protein ligand expressed on lymphocytes, B antigen-presenting considered key inhibitory checkpoint involved cancer regulation. immunohistochemical expression gynecological malignancies extremely variable based tumor stage molecular subtypes. As result, class monoclonal antibodies targeting PD-1 receptor PD-L1, known as inhibitors, found successful application clinical settings. In practice, standard method for identifying suitable candidates inhibitor therapy involves assessment tissues. The most commonly used assays trials are SP142, 28-8, 22C3, SP263, each which rigorously validated specific platforms. Gynecologic cancers encompass wide spectrum originating from ovaries, uterus, cervix, vulva. neoplasms shown immunotherapy appears be influenced genetic profiles, including factors such mismatch repair status, mutational burden, expression. present paper, an extensive review various gynecologic types discussed, providing guide pathological reporting.

Language: Английский

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Microenvironment-based immunotherapy in oral cancer: a comprehensive review

Medical Oncology, Journal Year: 2025, Volume and Issue: 42(5)

Published: March 28, 2025

Language: Английский

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DRG2 is required for surface localization of PD-L1 and the efficacy of anti-PD-1 therapy

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: May 27, 2024

Abstract More than half of tumor patients with high PD-L1 expression do not respond to anti-PD-1/PD-L1 therapy, and the underlying mechanisms are yet be clarified. Here we show that developmentally regulated GTP-binding protein 2 (DRG2) is required for response PD-L1-expressing tumors anti-PD-1 therapy. DRG2 depletion enhanced IFN-γ signaling increased level in melanoma cells. However, it inhibited recycling endosomal reduced surface levels, which led defects interaction PD-1. Anti-PD-1 did expand effector-like T cells within DRG2-depleted failed improve survival tumor-bearing mice. Cohort analysis revealed bearing low levels were resistant These findings identify as a key regulator therapy provide insights into how increase correlation between

Language: Английский

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Differentially Expressed MicroRNAs in Pre-Transplant Lung Biopsies Target Immune Checkpoint Proteins and can Predict Primary Graft Dysfunction in Lung Transplantation

Heliyon, Journal Year: 2025, Volume and Issue: 11(4), P. e42515 - e42515

Published: Feb. 1, 2025

Highlights•Immune checkpoints may be involved in the onset of lung graft dysfunction•Dysregulation miRNAs impact expression immune checkpoints•Evaluation before transplantation could offer prognostic benefitsAbstractLung (LTx) significantly improves outcomes for patients with end-stage respiratory failure. However, primary dysfunction (PGD) remains one most relevant hurdles. Although PGD is attributed to ischemia-reperfusion injury (IRI), responses, primarily T cell-mediated, play a pivotal role its pathogenesis. Additionally, innate activation following IRI links adaptive alloimmunity, highlighting early events on LTx outcomes. Immune (ICPs) such as PD-1/PD-L1, CD40/CD40LG, and OX40/OX40L, regulate post-LTx cell dysregulation microRNAs (miRNAs) has been implicated altering ICP expression, influencing amplification responses.In this preliminary study, we used taqMan low-density array (TLDA) cards investigate miRNA dysregulation's potential marker pre-transplant back-table biopsies. Our analysis revealed differential donor tissues, potentially associated onset, targeting regulatory pathways. Specifically, deregulated targeted key proteins, including PD-L1, CD40LG, OX40L. Moreover, these was observed grafts future compared without PGD, suggesting benefit possible tissue dysfunction.These findings provide basis investigations into their mechanistic roles therapeutic PGD. based limited number cases, our results imply that might dysfunction. While requiring validation larger cohorts, data raise possibility evaluation aforementioned markers during phase, monitoring use compounds can modulate function molecules evaluated management patients.Graphical abstract

Language: Английский

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Bibliometric insight into neoadjuvant immunotherapy in non-small cell lung cancer: trends, collaborations, and future avenues

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 10, 2025

Background Neoadjuvant immunotherapy (NIT) is a rapidly emerging paradigm for advanced resectable non-small cell lung cancer (NSCLC). However, there no bibliometric analysis in this research field. Objective To analyze the hotspots and trends of NIT NSCLC provide reference study China. Methods Retrieve literature related to from Web Science, PubMed, Scopus databases up September 10, 2024. Use CiteSpace VOSviewer software visualization keywords country, author, institution, literature. Results There were 1575 references, overall annual publication volume showed an upward trend; Forde Patrick M have published most articles The mainly focus on chemotherapy, NSCLC, immunotherapy, neoadjuvant pathological reactions, etc. Conclusions This first comprehensively summarizing NIT’s development NSCLC. Our assessment provides panoramic view milieu surrounding encapsulating present state, evolving trends, potential future directions, particularly emphasizing promise immunochemotherapy.

Language: Английский

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Molecular Mechanisms of Immune Regulation: A Review

Cells, Journal Year: 2025, Volume and Issue: 14(4), P. 283 - 283

Published: Feb. 14, 2025

The immune system must carefully balance fighting pathogens with minimization of inflammation and avoidance autoimmune responses. Over the past ten years, researchers have extensively studied mechanisms regulating this delicate balance. Comprehending these is essential for developing treatments inflammatory conditions. This review aims to synthesize knowledge immunoregulatory processes published from 2014-2024 highlight discoveries that provide fresh perspectives on complex keywords "molecular mechanisms", "immune regulation", signaling pathways", homeostasis" were used search PubMed articles between 2014 2024, a preference in three years. Recent research has pinpointed impact factors such as cytokine signaling, T-cell regulation, epigenetic immunometabolism function. New highlights intricate interactions other molecular elements. A key area interest non-coding RNAs metabolic pathways regulation Exploring by which regulated will new avenues address

Language: Английский

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Exploring Immune Checkpoint Inhibitors: Focus on PD-1/PD-L1 Axis and Beyond

Pathology - Research and Practice, Journal Year: 2025, Volume and Issue: 269, P. 155864 - 155864

Published: March 1, 2025

Language: Английский

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The cGAS-STING pathway in cancer immunity: dual roles, therapeutic strategies, and clinical challenges

Essays in Biochemistry, Journal Year: 2025, Volume and Issue: 69(02)

Published: March 7, 2025

The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is a crucial component the host's innate immunity and plays central role in detecting cytosolic double-stranded DNA from endogenous exogenous sources. Upon activation, cGAS synthesizes cGAMP, which binds to STING, triggering cascade immune responses, including production type I interferons pro-inflammatory cytokines. In context cancers, cGAS-STING can exert dual roles: on one hand, it promotes anti-tumor by enhancing antigen presentation, stimulating T-cell inducing direct tumor cell apoptosis. On other chronic particularly tumors with chromosomal instability, lead suppression progression. Persistent signaling results up-regulation checkpoint molecules such as PD-L1, contributing evasion metastasis. Consequently, strategies targeting have consider balance activation tolerance caused activation. This review explores mechanisms underlying both protumor roles pathway, focus potential therapeutic approaches, challenges faced their clinical application, along corresponding solutions.

Language: Английский

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Immunogenicity and Safety Profile of Two Adjuvanted-PD-L1-Based Vaccine Candidates in Mice, Rats, Rabbits, and Cynomolgus Monkeys

Vaccines, Journal Year: 2025, Volume and Issue: 13(3), P. 296 - 296

Published: March 11, 2025

Background: The therapeutic blockade of the PD1/PD-L1 axis with monoclonal antibodies has led to a breakthrough in cancer treatment, as it plays key role immune evasion tumors. Nevertheless, treating patients vaccines that stimulate targeted response is another attractive approach for which few side effects have been observed combination immunotherapy clinical trials. In this sense, our group recently developed vaccine candidate called PKPD-L1Vac contains an antigen extracellular domain human PD-L1 fused 47 amino-terminal, part LpdA gene N. meningitides, produced E. coli. investigation potential toxicities associated by new therapy preclinical studies critical optimizing efficacy and safety therapy. Methods: Here, we describe immunogenicity preliminary mice, rats, rabbits, non-human primates make use 200 μg dose PKPD-L1 VSSPs or alum phosphate contribute assessment adverse events are relevant future development program novel candidate. Results: administration four species at doses studied was immunogenic did not result behavioral, clinical, hematological, serum biochemical changes. Conclusions: Therefore, could be considered suitable further complex toxicological way its evaluation humans opened.

Language: Английский

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