PD-1 and PD-L1: architects of immune symphony and immunotherapy breakthroughs in cancer treatment

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

Published: Dec. 1, 2023

PD-1 (Programmed Cell Death Protein-1) and PD-L1 Ligand-1) play a crucial role in regulating the immune system preventing autoimmunity. Cancer cells can manipulate this system, allowing them to escape detection promote tumor growth. Therapies targeting PD-1/PD-L1 pathway have transformed cancer treatment demonstrated significant effectiveness against various types. This study delves into structure signaling dynamics of its ligands PD-L1/PD-L2, diverse inhibitors their efficacy, resistance observed some patients. Furthermore, explored challenges associated with inhibitor approach. Recent advancements combination immunotherapy chemotherapy, radiation, surgical procedures enhance patient outcomes also been highlighted. Overall, offers an in-depth overview significance future implications oncology.

Language: Английский

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Current Status in Rechallenge of Immunotherapy

International Journal of Biological Sciences, Journal Year: 2023, Volume and Issue: 19(8), P. 2428 - 2442

Published: Jan. 1, 2023

The treatment of malignant tumors has entered the era immunotherapy, and immune checkpoint inhibitors (ICIs) have brought significant benefits to patients.However, some patients are required discontinue with ICIs owing factors such as disease progression intolerable side effects.Faced limited subsequent options complex medical needs, we searched PubMed, Embase, Cochrane library, NIH clinical trials database found that ICI rechallenge could be a relevant strategy.The affect efficacy include patients' characteristics, therapeutic strategy selection, timing treatment.Multiple used identify target population, which features PD-L1 expression more potential.Both single combination therapy may survival benefits.Patients who tolerated initial immunotherapy well undergo rechallenge, while experienced grade 3 or higher immune-related adverse events should carefully assessed prior rechallenge.Interventions interval between two courses will clearly an impact on treatment.Preliminary data evaluation supports further investigation contribute its efficacy.

Language: Английский

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Spatiotemporal metabolomic approaches to the cancer-immunity panorama: a methodological perspective

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

Published: Sept. 18, 2024

Language: Английский

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The Interaction Between Vasculogenic Mimicry and the Immune System: Mechanistic Insights and Dual Exploration in Cancer Therapy

Cell Proliferation, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 26, 2025

ABSTRACT Vasculogenic mimicry (VM) represents a novel form of angiogenesis discovered in numerous malignant tumours recent years. Unlike traditional angiogenesis, VM facilitates tumour blood supply independently endothelial cells by enabling to functional vascular networks. This phenomenon, where replace tubular structures, plays pivotal role growth and metastasis. Tumour progression is influenced variety factors, including immune components. The system serves as critical defence mechanism identifying eliminating abnormal entities, such cells. inevitably reminds us the intricate connection between VM. Indeed, years, some studies have shown that responses related play different regulatory roles formation Therefore, this review provides comprehensive discussion on mechanisms underlying formation, its interplay with system, potential leveraging immunotherapy target

Language: Английский

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Efficacy and safety of first-line PD-1/PD-L1 inhibitor in combination with CTLA-4 inhibitor in the treatment of patients with advanced non-small cell lung cancer: a systemic review and meta-analysis

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

Published: Feb. 6, 2025

The combination of PD-1/PD-L1 inhibitor with CTLA-4 for advanced non-small cell lung cancer(NSCLC) is presently a significant area research, however its clinical application remains contentious. This meta-analysis aimed to assess the efficacy and safety first-line in (CP) treatment patients NSCLC. A systemic search was conducted four databases (PubMed, Cochrane library, Embase, Web Science) from their establishment until January 17, 2024, randomized controlled trials that investigated use plus Progression-free survival (PFS), overall (OS), objective response rate (ORR), disease control (DCR), adverse events (AEs) were subjected meta-analyses. Totally 7 eligible including 4682 people included. Two comparative analyses performed: CP versus chemotherapy, (P). Compared chemotherapy group, improved OS (HR: 0.84, 95% CI: 0.75-0.94, p<0.05) but not PFS 0.94, 95%CI: 0.73-1.20, p = 0.63) or ORR (OR: 1.16, 0.79-1.71, 0.45). In terms toxicity, had slightly fewer any AEs compared (RR: 0.91-0.97; p<0.05). P there no difference (MD: -0,25, -2.47-1.98, 0.83), -0.91, -3.19-1.36, 0.43), (OR:1.05, CI. 0.80-1.36, 0.73). Subgroup analysis revealed provided superior PD-L1 expression < 1%. feasible safe therapy Specifically, may function as therapeutic alternative individuals low negative expression, resulting enhanced long-term outcomes P. Further prolonged follow-up periods are necessary validate these results, particularly focusing on differing levels, improve stratified implementation immunotherapy. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024621116, identifier CRD42024621116.

Language: Английский

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Immuno-oncological Challenges and Chemoresistance in Veterinary Medicine: Probiotics as a New Strategic Tool

Probiotics and Antimicrobial Proteins, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 15, 2025

Language: Английский

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A Comparative Molecular Dynamics Study of Food-Derived Compounds as PD-L1 Inhibitors: Insights Across Six Flavonoid Subgroups

Molecules, Journal Year: 2025, Volume and Issue: 30(4), P. 907 - 907

Published: Feb. 15, 2025

In this study, we investigated the inhibitory potential of 60 flavonoids from six distinct subgroups on programmed cell death ligand 1 (PD-L1) dimer through molecular docking and dynamics simulations. Using AutoDock Vina for docking, binding poses affinities were evaluated, revealing an average affinity -8.5 kcal/mol flavonoids. Among them, ginkgetin exhibited highest free energy -46.73 kcal/mol, indicating a strong interaction with PD-L1, while diosmin followed closely, -44.96 kcal/mol. Molecular simulations used to further elucidate dynamic interactions stability flavonoid-PD-L1 complexes, analyses showing minimal root mean square deviation (RMSD) favorable fluctuation (RMSF) profiles several compounds, particularly formononetin, idaein, neohesperidin. Additionally, contact number hydrogen bond performed, which highlighted as key significant interactions, evidenced by their stable conformations robust throughout Ultimately, cell-based assay confirmed ability inhibit proliferation cancer cells. These results, validated assays, indicate that strategy identifying natural compounds anticancer activity using computational modeling is highly effective.

Language: Английский

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A phase I, open-label, multicentre, first-in-human study to evaluate safety, pharmacokinetics and efficacy of AMG 404, a PD-1 inhibitor, in patients with advanced solid tumours

BMJ Open, Journal Year: 2025, Volume and Issue: 15(5), P. e088578 - e088578

Published: May 1, 2025

Objective To evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary antitumour activity of AMG 404, a fully human IgG1 monoclonal antibody targeting programmed cell death-1, in patients with advanced solid tumours. Design First-in-human phase I study comprising eight dose expansion cohorts, including cohorts microsatellite instability-high (MSI-H) tumours non-small lung cancer high death-ligand 1 expression (NSCLC/PDL1-H, tumour proportion score ≥50%). Setting Conducted across 28 global sites. Participants This enrolled adult histologically or cytologically confirmed metastatic locally not amenable to curative treatment surgery radiation. The inclusion criteria included life expectancy >3 months, ≥1 measurable evaluable lesion per modified Response Evaluation Criteria Solid Tumours (RECIST) V.1.1, an Eastern Cooperative Oncology Group performance status ≤2 adequate haematological, renal hepatic function. Patients prior checkpoint inhibitors, primary brain untreated symptomatic metastases leptomeningeal disease history other malignancy within past 2 years were excluded. Interventions planned doses 240 mg, 480 mg 1050 404 administered every 4 weeks (Q4W). Primary secondary outcome measures endpoints dose-limiting toxicities (DLTs), treatment-emergent adverse events, treatment-related changes vital signs clinical laboratory tests. Secondary PK parameters, incidence antidrug (AMG 404) antibodies assessed RECIST V.1.1 (objective response, duration progression-free survival (PFS), control stable disease). Results A total 171 enrolled; 168 treated. Median (range) follow-up was 36.3 (1.6–137.1). No DLTs observed. Grade 3 serious events occurred 16 (9.5%) 12 (7.1%) patients, respectively. Q4W selected as recommended II dose. serum exposure increased approximately proportionally. objective response rate (80% CI) 19.6% (15.7–24.1) for overall population 36.6% (26.4–47.8) 30.8% (14.2–‍52.3) MSI-H (n=41) NSCLC/PDL1-H (n=13), 54.8% (49.5–59.9). median PFS 3.7 (3.5–4.5) months 14.8 (9.0–not estimable) 4.4 (2.2–9.7) NSCLC/PDL1-H, Conclusions monotherapy tolerable at tested doses, encouraging observed types. Trial registration number NCT03853109 .

Language: Английский

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N6-methyladenosine reader protein IGF2BP1 suppresses CD8 + T cells-mediated tumor cytotoxicity and apoptosis in colon cancer

APOPTOSIS, Journal Year: 2023, Volume and Issue: 29(3-4), P. 331 - 343

Published: Oct. 17, 2023

Language: Английский

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Fc–Fc interactions and immune inhibitory effects of IgG4: implications for anti-PD-1 immunotherapies

Journal for ImmunoTherapy of Cancer, Journal Year: 2024, Volume and Issue: 12(6), P. e009034 - e009034

Published: June 1, 2024

Background The majority of anti-programmed cell-death 1 (PD-1) monoclonal antibodies (mAbs) use S 228 P mutation IgG4 as the structural basis to avoid activation immune cells or complement. However, little attention has been paid Fc–Fc interactions between and other IgG Fc fragments that could result in adverse effects. Fc-null IgG1 framework is a potential safer alternative undesirable receptor binding derived effects observed with IgG4. This study provides comprehensive evaluation anti-PD-1 mAbs these two frameworks. Methods Trastuzumab rituximab (both IgG1), wildtype were immobilized on nitrocellulose membranes, coated microplates biosensor chips, bound tumor targets for interactions. Wildtype IgG4, mAb nivolumab (IgG4 P), penpulimab (Fc-null tislelizumab P-R 409 K) assessed their reactions proteins quantitative kinetic data obtained. To evaluate responses mediated by trastuzumab context combination therapy, we employed classic models antibody-dependent cellular cytotoxicity, phagocytosis, complement dependent cytotoxicity. Tumor-bearing mouse models, both humanized, used vivo investigation. Furthermore, also examined diverse cell populations Results Experiments demonstrated through interactions, diminishing cell-mediated cytotoxicity phagocytosis reactions. Quantitative analysis parameters suggests exhibit comparable affinities non-denatured denatured states. exerted inhibitory various types. promoted growth models. Conversely, IgG1, penpulimab, did not show similar Conclusions represents choice immunotherapies avoiding Fc-related K displayed properties benefits. contributes understanding immunotherapy resistance advancement therapies cancer.

Language: Английский

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