Cutaneous manifestations associated with immune checkpoint inhibitors

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Фев. 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.

Язык: Английский

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Gut microbiome for predicting immune checkpoint blockade-associated adverse events

Genome Medicine, Год журнала: 2024, Номер 16(1)

Опубликована: Янв. 19, 2024

Abstract Background The impact of the gut microbiome on initiation and intensity immune-related adverse events (irAEs) prompted by immune checkpoint inhibitors (ICIs) is widely acknowledged. Nevertheless, there inconsistency in microbial associations with irAEs reported across various studies. Methods We performed a comprehensive analysis leveraging dataset that included published data ( n = 317) in-house generated from 16S rRNA shotgun metagenome samples 115). utilized machine learning-based approach, specifically Random Forest (RF) algorithm, to construct microbiome-based classifier capable distinguishing between non-irAEs irAEs. Additionally, we conducted analysis, integrating transcriptome profiling, explore potential underlying mechanisms. Results identified specific species patients experiencing non-irAEs. RF classifier, developed using 14 features, demonstrated robust discriminatory power (AUC 0.88). Moreover, predictive score our exhibited significant discriminative capability for identifying two independent cohorts. Our functional revealed altered was characterized an increased menaquinone biosynthesis, accompanied elevated expression rate-limiting enzymes menH menC . Targeted metabolomics further highlighted notably higher abundance serum who did not develop compared group. Conclusions study underscores biomarkers predicting onset highlights menaquinone, metabolite derived community, as possible selective therapeutic agent modulating occurrence

Язык: Английский

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Cutaneous Adverse Events Associated with Immune Checkpoint Inhibitors: A Review Article

Current Oncology, Год журнала: 2022, Номер 29(4), С. 2871 - 2886

Опубликована: Апрель 18, 2022

Immune checkpoint inhibitors (ICIs) have emerged as novel options that are effective in treating various cancers. They monoclonal antibodies target cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death 1 (PD-1), and death-ligand (PD-L1). However, activation of the immune systems through ICIs may concomitantly trigger a constellation immunologic symptoms signs, termed immune-related adverse events (irAEs), with skin being most commonly involved organ. The dermatologic toxicities observed nearly half patients treated ICIs, mainly form maculopapular rash pruritus. In majority cases, these cutaneous irAEs self-limiting manageable, continuation is possible. This review provides an overview variable ICI-mediated reactions describes clinical histopathologic presentation. Early accurate diagnosis, recognition severe toxicities, appropriate management key goals to achieve favorable outcomes quality life cancer patients.

Язык: Английский

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Nano-immunotherapy: overcoming delivery challenge of immune checkpoint therapy

Journal of Nanobiotechnology, Год журнала: 2023, Номер 21(1)

Опубликована: Сен. 21, 2023

Abstract Immune checkpoint (ICP) molecules expressed on tumor cells can suppress immune responses against tumors. ICP therapy promotes anti-tumor by targeting inhibitory and stimulatory pathways of like T dendritic (DC). The investigation into the combination therapies through novel inhibitors (ICIs) has been limited due to immune-related adverse events (irAEs), low response rate, lack optimal strategy for combinatorial cancer immunotherapy (IMT). Nanoparticles (NPs) have emerged as powerful tools promote multidisciplinary cooperation. feasibility efficacy targeted delivery ICIs using NPs overcome primary barrier, improve therapeutic efficacy, provide a rationale more clinical investigations. Likewise, conjugate or encapsulate ICIs, including antibodies, RNAs, small molecule inhibitors. Therefore, combining drug system (DDS) with could profitable immunotherapeutic treatment. This article reviews significant controlled DDS current data from pre-clinical trials mono- IMT limitations. Graphical

Язык: Английский

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A fractional-order mathematical model for lung cancer incorporating integrated therapeutic approaches

Scientific Reports, Год журнала: 2023, Номер 13(1)

Опубликована: Авг. 1, 2023

This paper addresses the dynamics of lung cancer by employing a fractional-order mathematical model that investigates combined therapy surgery and immunotherapy. The significance this study lies in its exploration effects immunotherapy on tumor growth rate immune response to cells. To optimize treatment dosage based response, feedback control system is designed using theory, Pontryagin's Maximum Principle utilized derive necessary conditions for optimality. results reveal reproduction number [Formula: see text] 2.6, indicating cell would generate 2.6 new cells during lifetime. coefficient 0.22, signifying divide at 0.22 times normal simulations demonstrate approach yields significantly improved patient outcomes compared either alone. Furthermore, analysis highlights sensitivity steady-state solution variations (the division stem cells) differentiation into progenitor cells). research offers clinicians valuable tool developing personalized plans patients, incorporating individual factors characteristics. novelty work integration surgery, immunotherapy, extending beyond previous efforts literature.

Язык: Английский

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Implication of the Gut Microbiome and Microbial-Derived Metabolites in Immune-Related Adverse Events: Emergence of Novel Biomarkers for Cancer Immunotherapy

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(3), С. 2769 - 2769

Опубликована: Фев. 1, 2023

Immune checkpoint inhibitors (ICIs) have changed how we think about tumor management. Combinations of anti-programmed death ligand-1 (PD-L1) immunotherapy become the standard care in many advanced-stage cancers, including as a first-line therapy. Aside from improved anti-tumor immunity, mechanism action immune exposes new toxicity profile known immune-related adverse effects (irAEs). This novel can damage any organ, but skin, digestive and endocrine systems are most frequently afflicted. Most ICI-attributed symptoms mild, some severe necessitate multidisciplinary side effect Obtaining knowledge on various forms toxicities swiftly changing treatment techniques to lower probability experiencing irAEs has priority oncological care. In recent years, there been growing understanding an intriguing link between gut microbiome ICI outcomes. Multiple studies demonstrated connection microbial metagenomic metatranscriptomic patterns efficacy malignant melanoma, lung colorectal cancer. The immunomodulatory real biological background well. Furthermore, specific signatures metabolites might be associated with onset severity symptoms. By identifying these factors, biomarkers used clinical practice predict manage potential irAEs. comprehensive review aims summarize aspects ICI-related their association metabolome. We aim explore current state important reliable irAE-related origin discuss toxicity.

Язык: Английский

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Antiviral therapy can effectively suppress irAEs in HBV positive hepatocellular carcinoma treated with ICIs: validation based on multi machine learning

Frontiers in Immunology, Год журнала: 2025, Номер 15

Опубликована: Янв. 27, 2025

Background Immune checkpoint inhibitors have proven efficacy against hepatitis B-virus positive hepatocellular. However, Immunotherapy-related adverse reactions are still a major challenge faced by tumor immunotherapy, so it is urgent to establish new methods effectively predict immunotherapy-related reactions. Objective Multi-machine learning model were constructed screen the risk factors for irAEs in ICIs treatment of HBV-related hepatocellular and build prediction occurrence clinical IRAEs. Methods Data from 274 B virus patients who received PD-1 or/and CTLA4 inhibitor had immune cell detection results collected Henan Cancer Hospital retrospective analysis. Models established using Lasso, RSF (RandomForest), xgBoost, with ten-fold cross-validation resampling used ensure reliability. The impact influencing on (immune-related events) was validated Decision Curve Analysis (DCA). Both uni/multivariable analysis accomplished Chi-square/Fisher’s exact tests. accuracy verified DCA curve. Results A total liver cancer enrolled study. Predictive models three machine algorithms analyze statistically evaluate characteristics, including data. Lasso regression 0.864, XGBoost achieved 0.903, RandomForest reached 0.961. Resampling internal validation revealed that highest recall rate (AUC = 0.892). Based learning-selected indicators, antiviral therapy HBV DNA copy number showed significant correlation both severity irAEs. Antiviral notably reduced incidence IRAEs may modulate these events through regulation cells. also demonstrated strong predictive performance. Effective control viral load significantly mitigates Conclusion show therapeutic potential HBV-HCC. Following therapy, severe decreases. Even cases where incomplete, continuous can mitigate

Язык: Английский

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

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Янв. 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.

Язык: Английский

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Update in TIGIT Immune-Checkpoint Role in Cancer

Frontiers in Oncology, Год журнала: 2022, Номер 12

Опубликована: Май 17, 2022

The in-depth characterization of cross-talk between tumor cells and T in solid hematological malignancies will have to be considered develop new therapeutical strategies concerning the reactivation maintenance patient-specific antitumor responses within patient microenvironment. Activation immune depends on a delicate balance activating inhibitory signals mediated by different receptors. cell immunoreceptor with immunoglobulin ITIM domain (TIGIT) is an receptor expressed regulatory (Tregs), activated cells, natural killer (NK) cells. TIGIT pathway regulates cell-mediated recognition vivo vitro represents exciting target for checkpoint blockade immunotherapy. as monotherapy or combination other inhibitor receptors drugs emerging clinical trials patients cancer. purpose this review update role cancer progression, looking at pathways that are often upregulated possible therapeutic avoid aggressiveness, drug resistance, treatment side effects. However, first part, we overviewed checkpoints immunoediting, structure ligands, summarized key express TIGIT.

Язык: Английский

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Neutrophil extracellular traps (NETs)-related lncRNAs signature for predicting prognosis and the immune microenvironment in breast cancer

Frontiers in Cell and Developmental Biology, Год журнала: 2023, Номер 11

Опубликована: Фев. 2, 2023

Background: Neutrophil extracellular traps (NETs) are closely associated to tumorigenesis and development. However, the relationship between NETs-related long non-coding RNAs (lncRNAs) characteristics of breast tumor remains an enigma. This study aimed explore clinical prognostic value lncRNAs, their correlation with microenvironment (TME) predictive ability drug sensitivity in patients cancer (BC). Methods: The expression profiles RNA-sequencing relevant data BC were extracted from TCGA database. co-expression network analysis, univariable, least absolute shrinkage selection operator (LASSO) multivariable Cox algorithms employed construct lncRNAs signature. A nomogram was established validated application. Furthermore, immune for different risks explored. Finally, pattern using qRT-PCR tissues adjacent non-cancerous tissues. Results: Based on a risk model consisted 10 (SFTA1P, ACTA2-AS1, AC004816.2, AC000067.1, LINC01235, LINC01010, AL133467.1, AC092919.1, AL591468.1, MIR200CHG) established. Kaplan-Meier analysis showed that overall survival (OS) significantly better low-risk than high-risk (Ptraining cohort < 0.001, Pvalidation = 0.009). also good accuracy OS individuals both training validation cohorts. function enrichment revealed group mainly enriched immune-related functions pathways, mutation burden this markedly higher (p 0.022). Moreover, significant differences observed cells, checkpoint genes among at 0.05). response chemotherapeutic agents immunotherapy related 0.001). experimental generally consistent bioinformatics results. Conclusion: Our provided novel yielded strong scientific rationale individualized treatment strategies, elucidating patients.

Язык: Английский

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