Regulatory mechanisms of PD-1/PD-L1 in cancers

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: May 18, 2024

Abstract Immune evasion contributes to cancer growth and progression. Cancer cells have the ability activate different immune checkpoint pathways that harbor immunosuppressive functions. The programmed death protein 1 (PD-1) cell ligands (PD-Ls) are considered be major molecules. interaction of PD-1 PD-L1 negatively regulates adaptive response mainly by inhibiting activity effector T while enhancing function regulatory (Tregs), largely contributing maintenance homeostasis prevents dysregulated immunity harmful responses. However, exploit PD-1/PD-L1 axis cause escape in development Blockade neutralizing antibodies restores enhances anti-tumor immunity, achieving remarkable success therapy. Therefore, mechanisms cancers attracted an increasing attention. This article aims provide a comprehensive review roles signaling human autoimmune diseases cancers. We summarize all aspects underlying expression cancers, including genetic, epigenetic, post-transcriptional post-translational mechanisms. In addition, we further progress clinical research on antitumor effects targeting alone combination with other therapeutic approaches, providing new strategies for finding tumor markers developing combined approaches.

Language: Английский

---

The role of PD-1 signaling in health and immune-related diseases

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: May 16, 2023

Programmed cell death 1 receptor (PD-1) and its ligands constitute an inhibitory pathway to mediate the mechanism of immune tolerance provide homeostasis. Significantly, binding partners PD-1 associated are diverse, which facilitates immunosuppression in cooperation with other checkpoint proteins. Accumulating evidence has demonstrated important immunosuppressive role axis tumor microenvironment autoimmune diseases. In addition, blockades have been approved treat various cancers, including solid tumors hematological malignancies. Here, we a comprehensive review pathway, focusing on structure expression PD-1, programmed ligand (PD-L1), 2 (PD-L2); diverse biological functions signaling health immune-related diseases (including immunity, autoimmunity, infectious transplantation allergy privilege); adverse events related PD-L1 inhibitors.

Language: Английский

---

Cutaneous manifestations associated with immune checkpoint inhibitors

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 20, 2023

Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that block key mediators of tumor-mediated immune evasion. The frequency its use has increased rapidly and extended to numerous cancers. ICIs target molecules, such as programmed cell death protein 1 (PD-1), PD ligand (PD-L1), T activation, including cytotoxic T-lymphocyte-associated protein-4 (CTLA-4). However, ICI-driven alterations in the system can induce various immune-related adverse events (irAEs) affect multiple organs. Among these, cutaneous irAEs most common often first develop. Skin manifestations characterized by a wide range phenotypes, maculopapular rash, psoriasiform eruption, lichen planus-like pruritus, vitiligo-like depigmentation, bullous diseases, alopecia, Stevens-Johnson syndrome/toxic epidermal necrolysis. In terms pathogenesis, mechanism remains unclear. Still, several hypotheses have been proposed, activation cells against antigens normal tissues tumor cells, release proinflammatory cytokines associated with effects specific tissues/organs, association human leukocyte antigen variants organ-specific irAEs, acceleration concurrent medication-induced drug eruptions. Based on recent literature, this review provides an overview each ICI-induced skin manifestation epidemiology focuses mechanisms underlying irAEs.

Language: Английский

---

Molecular Mechanisms of Cutaneous Immune-Related Adverse Events (irAEs) Induced by Immune Checkpoint Inhibitors

Current Oncology, Journal Year: 2023, Volume and Issue: 30(7), P. 6805 - 6819

Published: July 18, 2023

Over the past few decades, immune checkpoint inhibitors (ICIs) have emerged as promising therapeutic options for treatment of various cancers. These novel treatments effectively target key mediators pathways. Currently, ICIs primarily consist monoclonal antibodies that specifically block cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death 1 (PD-1), death-ligand (PD-L1), and lymphocyte activation gene 3 protein (LAG-3). Despite notable efficacy in cancer treatment, they can also trigger immune-related adverse events (irAEs), which present autoimmune-like or inflammatory conditions. IrAEs potential to affect multiple organ systems, with cutaneous toxicities being most commonly observed. Although irAEs are typically low-grade severity usually be managed effectively, there cases where severe become life-threatening. Therefore, early recognition a comprehensive understanding mechanisms underlying crucial improving clinical outcomes patients. However, precise pathogenesis remains unclear. This review focuses on skin manifestations induced by ICIs, prognosis related irAEs, exploration involved irAEs.

Language: Английский

---

Immune-related adverse events with PD-1/PD-L1 inhibitors: insights from a real-world cohort of 2523 patients

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

Published: Jan. 31, 2025

Immune checkpoint inhibitors (ICIs) have significantly changed cancer therapy, improving patient survival rates and clinical outcomes. Nevertheless, the use of PD-1/PD-L1 can result in immune-related adverse events (irAEs). This study aims to investigate prevalence associated risk factors irAEs a real-world setting, as well assess their effects on optimal therapeutic A retrospective analysis involved 2523 patients with who received inpatient treatment between January 2018 December 2022. We documented patients' demographic characteristics, PD-1 or PD-L1 inhibitors, modalities, incidences, timing, severity irAEs, efficacy outcomes by reviewing records. Patients were categorized into an group non-irAEs group, former further subdivided multiple single irAE group. Chi-square tests employed evaluate differences baseline characteristics groups, groups. Additionally, logistic regression was utilized identify linked irAEs. Among eligible patients, 1096 reported 1802 incidence 43.4%. individuals, 92.1% classified grade 1-2, while 7.9% 3 higher. IrAEs affected various organ systems, endocrine toxicity (17.7%), hepatic (17.2%), hematologic (11.4%) being most common. 20.5% experienced multi-system The average time for develop within four cycles. Significant gender, age, Eastern Cooperative Oncology Group (ECOG) Performance Status (PS), comorbidities, modalities observed but not Compared exhibited higher objective response rate (ORR) disease control (DCR), also showed ORR than indicated that occurrence is related ECOG PS, modalities. may be better benefits.

Language: Английский

---

Oral Complications from Oropharyngeal Cancer Therapy

Cancers, Journal Year: 2023, Volume and Issue: 15(18), P. 4548 - 4548

Published: Sept. 14, 2023

Post-oropharyngeal cancer treatment complications include a multitude of oral side effects that impact overall survival and quality life. These acute chronic conditions affecting the cavity head neck, such as mucositis, infection, xerostomia, dysgeusia, radiation caries, osteonecrosis, trismus. This review will summarize most common from oropharyngeal therapy. The authors would like to point out literature cited frequently combines neck results. If recommendations are made strictly related cancers, this be highlighted.

Language: Английский

---

Association of the CD4+/CD8+ ratio with response to PD-1 inhibitor-based combination therapy and dermatological toxicities in patients with advanced gastric and esophageal cancer

International Immunopharmacology, Journal Year: 2023, Volume and Issue: 123, P. 110642 - 110642

Published: July 25, 2023

The host immune system affects the treatment response to checkpoint inhibitors and can be reflected by circulating cells. This study aimed evaluate whether T cell subtypes are correlated with clinical dermatological toxicities in patients advanced gastric esophageal cancer receiving PD-1 inhibitor-based combination therapy (n = 203). In training cohort, Eastern Cooperative Oncology Group performance status (ECOG PS), PD-L1 expression, antibiotic use, CD4+/CD8+ ratio were identified as independent prognostic factors these patients, using a Cox regression model. A nomogram predict overall survival (OS) probabilities was constructed factors. showed good discrimination ability (C-index, 0.767) externally confirmed validation test cohorts. Kaplan-Meier analysis that median OS ≥1.10 6.2 months, which significantly shorter than <1.10 (P < 0.001). Patients had superior objective (43.8% vs. 23.1%) disease control (72.9% 59.0%) rate, relative those ≥ 1.10. addition, corticosteroid independently toxicities. conclusion, baseline is potential factor for treated therapy, incorporating ratio, ECOG PS, use considerable accuracy.

Language: Английский

---

Emerging Insights into Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Induced by Immune Checkpoint Inhibitor and Tumor-Targeted Therapy

Journal of Inflammation Research, Journal Year: 2024, Volume and Issue: Volume 17, P. 2337 - 2351

Published: April 1, 2024

Anticancer drugs have revolutionized tumor therapy, with cutaneous toxicities such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) being common immune-related adverse events. The debate over the efficacy of systemic corticosteroids in treating these conditions persists, while necrosis factor (TNF)-alpha inhibitors show promise. This study aims to evaluate effectiveness safety combination therapy involving TNF-α inhibitor adalimumab for SJS/TEN induced by anticancer drugs. A literature review cases from 1992 2023 was conducted, alongside an analysis patients admitted First Affiliated Hospital Fujian Medical University during same period. Clinical characteristics, skin healing time, mortality, events were evaluated two treatment groups: treated targeted therapies immunotherapies. Among 27 studied (18 SJS or SJS-TEN overlapping 9 TEN), significantly reduced mucocutaneous reepithelization time duration compared corticosteroid monotherapy. Patients receiving combined had lower actual mortality rates than those on also showed a trend towards reducing standardized based Score Toxic Epidermal Necrolysis (SCORTEN). findings suggest that provides significant clinical benefits is safer alone contributes valuable insights into potential strategies severe reactions drugs, highlighting importance exploring alternative managing effectively.

Language: Английский

---

PD-1/PD-L1 Inhibitor - Related Adverse Events and Their Management in Breast Cancer

Journal of Cancer, Journal Year: 2024, Volume and Issue: 15(9), P. 2770 - 2787

Published: Jan. 1, 2024

As the positive results of multiple clinical trials were released, Programmed cell death 1 (PD-1) and ligand (PD-L1) inhibitors emerge as focus integrative breast cancer treatment.PD-1/PD-L1 are often used a sequential agent to be combined with other agents such chemotherapeutic agents, targeted radiation therapy.As therapies administered simultaneously or in sequence, they prone variety adverse effects on patients while achieving efficacy.It is challenge for clinicians maintaining balance between immune-related effects(irAEs) treatment efficacy.Previous literatures have paid lots attention caused by immunosuppressive themselves, there dearth research management immune during combination immunotherapy treatments.In this review, we discuss overall incidence irAEs PD-1/PD-L1 various types treatments cancer, including chemotherapy, CTLA-4 inhibitors, therapy, radiotherapy, systematically summarizes each organ-related reaction.It important emphasize that event neurological, hematologic, cardiac toxicity, no alternative but terminate immunotherapy.Thus, seeking more effective strategy irAEs' imminent urged raise awareness reactions.

Language: Английский

---

Symptom clusters and their impacts on the quality of life of patients with lung cancer receiving immunotherapy: A cross‐sectional study

Journal of Clinical Nursing, Journal Year: 2024, Volume and Issue: unknown

Published: June 17, 2024

Abstract Aim The objective of this study was to identify symptom clusters in lung cancer patients receiving immunotherapy and explore their impact on the quality life patients. Background Immunotherapy is widely used cancer; however, there little understanding impacts population. Design Cross‐sectional study. Methods survey contained Memorial Symptom Assessment Scale (MSAS), Quality Life Questionnaire‐Lung Cancer 43 a self‐designed General Information Evaluation Form. were identified using exploratory factor analysis (EFA) based scores. Spearman correlation performed evaluate associations between each cluster patients' life. Multiple linear regression employed examine This adhered STROBE guidelines. Results In total, 240 participants completed survey. Five named according characteristics: emotional‐related cluster, cancer‐related physical skin neural cluster. All clusters, except for had significantly detrimental patient Conclusion Lung undergoing experience range symptoms, which can be categorized into five clusters. These have negative Future research should focus developing interventions influencing factors. Patient or Public Contribution data collection phase, recruited participate

Language: Английский

---