A decade of checkpoint blockade immunotherapy in melanoma: understanding the molecular basis for immune sensitivity and resistance

Nature Immunology, Journal Year: 2022, Volume and Issue: 23(5), P. 660 - 670

Published: March 3, 2022

Language: Английский

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Immunomodulatory Precision: A Narrative Review Exploring the Critical Role of Immune Checkpoint Inhibitors in Cancer Treatment

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(10), P. 5490 - 5490

Published: May 17, 2024

An immune checkpoint is a signaling pathway that regulates the recognition of antigens by T-cell receptors (TCRs) during an response. These checkpoints play pivotal role in suppressing excessive responses and maintaining homeostasis against viral or microbial infections. There are several FDA-approved inhibitors (ICIs), including ipilimumab, pembrolizumab, avelumab. ICIs target cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death 1 (PD-1), ligand (PD-L1). Furthermore, ongoing efforts focused on developing new with emerging potential. In comparison to conventional treatments, offer advantages reduced side effects durable responses. growing interest potential combining different chemotherapy, radiation therapy, targeted therapies. This article comprehensively reviews classification, mechanism action, application, combination strategies various cancers discusses their current limitations. Our objective contribute future development more effective anticancer drugs targeting checkpoints.

Language: Английский

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Clinical Features, Immunopathogenesis, and Therapeutic Strategies in Vitiligo

Clinical Reviews in Allergy & Immunology, Journal Year: 2021, Volume and Issue: 61(3), P. 299 - 323

Published: July 20, 2021

Language: Английский

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Variation of the essential oil components of Citrus aurantium leaves upon using different distillation techniques and evaluation of their antioxidant, antidiabetic, and neuroprotective effect against Alzheimer’s disease

BMC Complementary Medicine and Therapies, Journal Year: 2024, Volume and Issue: 24(1)

Published: Feb. 2, 2024

Abstract Citrus fruit essential oil is considered one of the widely studied oils while its leaves attract less attention although being rich in nearly same composition as peel and flowers. The bitter orange or sour ( aurantium L.) were extracted using three different techniques namely; hydrodistillation (HD), steam distillation (SD), microwave-assisted (MV) to compare their chemical composition. samples analyzed through GC/FID GC/MS analyses. tested vitro antioxidant (DPPH, ABTS, CUPRAC, FRAP, PBD, MCA), neuroprotective enzyme inhibitory activities (acetylcholine butyl choline enzymes), antidiabetic (α-amylase α-glucosidase). results showed that thirty-five volatile ingredients detected quantified. Monoterpenes represented most abundant class followed by sesquiterpenes. C. carried potential activity where SD exhibited highest activity, with values arranged following order: FRAP (200.43 mg TE/g), CUPRAC (138.69 ABTS (129.49 DPPH (51.67 TE/g). also presented potent α-amylase (0.32) inhibition MV α-glucosidase (2.73 mmol ACAE/g), HD (2.53 (2.46 ACAE/g). BChE AChE (3.73 2.06 GALAE/g), respectively). Thus, can act a source antioxidant, antidiabetic, for future drug leads.

Language: Английский

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Candidate approaches for predicting vitiligo recurrence: an effective model and biomarkers

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

Published: Feb. 6, 2025

Vitiligo is a challenging chronic condition with unpredictable disease course and high propensity for relapse post-treatment. Recent studies have reported the biomarkers activity, severity, therapeutic response of vitiligo, yet very few investigated cytokines as predictive recurrence in vitiligo. This study aims to explore that serve extend research on factors related disease's activity. 92 patients 40 healthy controls were recruited at Air Force Medical Center from September 20, 2023, November 30, 2023. Ultrasensitive multiplex cytokine array was used measure plasma concentrations cytokines, including IFN-γ, CXCL9, CXCL10, CXCL11, IL-6, IL-15. IL-15 expressed higher levels circulation both segmental non-segmental vitiligo compared (p < 0.001). There no significant differences these between two types CXCL9 associated activity = 0.027). Correlation analysis showed positive relationship recurrent The expression IL-6 significantly than cases persistent stable 0.001, p 0.003, 0.002, 0.026, respectively), ROC demonstrating their capability recurrence, AUC values 0.806, 0.773, 0.896, 0.785, 0.709, respectively. Multivariate logistic regression model IFN-γ an independent predictor [OR (95%CI) =1.051 (1.012~1.116)], prediction accuracy 90.5% (38/42) training dataset 88.9% (16/18) testing dataset. Plasma CXCL11 might be potential also Additionally, multivariate demonstrated could candidate approach predicting recurrence.

Language: Английский

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A novel mouse model for checkpoint inhibitor-induced adverse events

PLoS ONE, Journal Year: 2021, Volume and Issue: 16(2), P. e0246168 - e0246168

Published: Feb. 11, 2021

Immune checkpoint inhibitors have demonstrated significant efficacy in the treatment of a variety cancers, however their therapeutic potential is limited by abstruse immune related adverse events. Currently, no robust animal model exists inhibitor-induced Establishing such will improve our mechanistic understanding this process, which turn inform design improved therapies. We developed mouse to determine inflammatory toxicities response dual blockade presence syngeneic tumors. Mice from susceptible genetic backgrounds received intraperitoneal injections anti-mouse PD-1 and CTLA-4 antibodies. The mice were monitored for weight loss histologic evidence inflammation. Blood was collected basic metabolic panels titers anti-nuclear In parallel, also treated with prednisolone, commonly used treat events among cancer patients. Among all backgrounds, B6/lpr anti-CTLA-4 anti-PD-1 antibodies more substantial hepatitis, pancreatitis, colitis, pneumonitis characterized organ infiltration cells. that tissue high serum levels glucose Finally, while administration prednisolone prevented development events, it abrogated protective anti-tumor effect checkout inhibitors. Genetic background modalities jointly modified tumor bearing mice, suggesting complex mechanism inhibitor-related Future studies assess additional susceptibility factors examine possible contributions other anti-inflammatory drugs.

Language: Английский

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Prognostic role of soluble PD-1 and BTN2A1 in overweight melanoma patients treated with nivolumab or pembrolizumab: finding the missing links in the symbiotic immune-metabolic interplay

Therapeutic Advances in Medical Oncology, Journal Year: 2023, Volume and Issue: 15

Published: Jan. 1, 2023

Individual response to immune checkpoint inhibitors (ICIs) is currently unpredictable in patients with melanoma. Recent findings highlight a striking improvement the clinical outcomes of overweight/obese treated ICIs, which seems driven, at least part, by programmed cell death protein 1 (PD-1)-mediated T-cell dysfunction. A putative role butyrophilins (BTNs) under investigation as novel mechanism cancer evasion and obesity-associated inflammation. This study investigates baseline plasma levels soluble PD-1 (sPD-1), ligand (sPD-L1), BTN2A1 (sBTN2A1), BTN3A1 (sBTN3A1), along body mass index (BMI), predictive biomarkers immunotherapy metastatic melanoma nivolumab or pembrolizumab first-line treatment. In all, 41 were included study. The level sPD-1 was significantly lower, sBTN2A1 higher, long-responder (median sPD-1: 10.3 ng/ml versus 16.6 ng/ml, p = 0.001; median sBTN2A1: 4.4 3.77 0.004). Lower higher also associated better overall rate. Notably, when we further stratified cohort using BMI sPD-1, ⩾ 25 < 11.24 had longer time treatment failure after inhibitor than other subgroups (p 0.001). Circulating detection, BMI, could give more insights into immune-metabolic interactions underlying benefit observed patients, improving use dynamic, noninvasive, for patient selection.

Language: Английский

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B cell profiles, antibody repertoire and reactivity reveal dysregulated responses with autoimmune features in melanoma

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: June 8, 2023

B cells are known to contribute the anti-tumor immune response, especially in immunogenic tumors such as melanoma, yet humoral immunity has not been characterized these cancers detail. Here we show comprehensive phenotyping samples of circulating and tumor-resident well serum antibodies melanoma patients. Memory enriched compared blood paired feature distinct antibody repertoires, linked specific isotypes. Tumor-associated undergo clonal expansion, class switch recombination, somatic hypermutation receptor revision. Compared with blood, tumor-associated produce proportionally higher levels unproductive sequences complementarity determining region 3 properties. The observed features signs affinity maturation polyreactivity suggest an active aberrant autoimmune-like reaction tumor microenvironment. Consistent this, tumor-derived polyreactive by autoantigen recognition. Serum reactivity antigens attributed autoimmune diseases cancer, their patients disease post-resection state. Our findings thus reveal cell lineage dysregulation repertoire specificity, alongside clonally-expanded tumor-infiltrating features, shaping response melanoma.

Language: Английский

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A comprehensive outline of the role of non-coding RNAs in vitiligo

Biochemistry and Biophysics Reports, Journal Year: 2025, Volume and Issue: 41, P. 101916 - 101916

Published: Jan. 9, 2025

Language: Английский

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Incidence and Outcome of Neurologic Immune-Related Adverse Events Associated With Immune Checkpoint Inhibitors in Patients With Melanoma

Neurology, Journal Year: 2023, Volume and Issue: 101(24)

Published: Aug. 31, 2023

Neurologic immune-related adverse events (n-irAEs) reportedly occur in up to 8% of patients treated with immune checkpoint inhibitors (ICIs) all age groups. We investigated the association between and n-irAEs ICIs examined effect on survival outcomes a large cohort melanoma.

Language: Английский

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