MIF and CD74 as Emerging Biomarkers for Immune Checkpoint Blockade Therapy

Cancers, Journal Year: 2024, Volume and Issue: 16(9), P. 1773 - 1773

Published: May 4, 2024

Immune checkpoint blockade (ICB) therapy is used to treat a wide range of cancers; however, some patients are at risk developing treatment resistance and/or immune-related adverse events (irAEs). Thus, there great need for the identification reliable predictive biomarkers response and toxicity. The cytokine MIF (macrophage migration inhibitory factor) its cognate receptor CD74 intimately connected with cancer progression have previously been proposed as prognostic patient outcome in various cancers, including solid tumors such malignant melanoma. Here, we assess their potential ICB irAE development. We provide brief overview function roles context autoimmune disease. also review evidence showing that may be use highlight careful consideration required when assessing serum levels biomarker due reported circadian expression human plasma. Finally, suggest future directions establishment development guide further research this field.

Language: Английский

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Development and validation of nomogram models for predicting immune-related adverse events in recurrent and metastatic nasopharyngeal carcinoma patients treated with PD-L1 inhibitors

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: March 13, 2025

Objective To predict the incidence of immune-related Adverse Events (irAEs) in patients with recurrent or metastatic Nasopharyngeal Carcinoma (NPC) treated Programmed Death-Ligand 1 (PD-L1) inhibitors, this study developed and validated nomogram models incorporating demographic, clinical, biological variables. Methods Data from 153 NPC were analyzed, variables including age, sex, Body Mass Index (BMI), clinical stage, biomarkers. Predictive constructed using multivariable logistic regression, Least Absolute Shrinkage Selection Operator (LASSO) Ridge regression. The models’ performance was evaluated Receiver Operating Characteristic (ROC) curves, calibration Decision Curve Analysis (DCA). Internal validation conducted through k-fold cross-validation. Results Independent predictors irAEs included PD-L1, Free Thyroxine (FT4), Sodium (Na), lymphocyte counts. Of three models, stepwise regression model performed best, an area under curve (AUC) 0.78. Calibration curves showed a strong correlation between predicted observed outcomes, DCA demonstrated high utility. Conclusion effectively PD-L1 inhibitors. Early identification elevated abnormal FT4, Na, irregular counts allows for closer monitoring personalized treatment, potentially improving outcomes. Further research is required to confirm these findings across other cancer types therapies.

Language: Английский

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Combination therapy with immune checkpoint inhibitors in colorectal cancer: Challenges, resistance mechanisms, and the role of microbiota

Biomedicine & Pharmacotherapy, Journal Year: 2025, Volume and Issue: 186, P. 118014 - 118014

Published: March 31, 2025

Language: Английский

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Evaluation of tumorous LCP1 and ADPGK as predictive biomarker for immune-related adverse events in bone and soft tissue sarcomas treated with anti-PD-1 and anti-PD-L1 antibodies

BMC Cancer, Journal Year: 2025, Volume and Issue: 25(1)

Published: April 7, 2025

Language: Английский

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Systemic immune characteristics predicting toxicity to immune checkpoint inhibitors in patients with advanced breast cancer

Journal of Autoimmunity, Journal Year: 2025, Volume and Issue: 153, P. 103423 - 103423

Published: April 22, 2025

Immune checkpoint inhibitors (ICIs) are among the most promising treatment options for cancer. However, frequent and sometimes life-threatening immune-related adverse events (irAEs) associated with ICI treatment. Therefore, it is imperative to establish a model predicting risk of irAEs identify high-risk groups, enable more accurate clinical risk‒benefit analysis decrease incidence irAEs. no ideal has been applied in practice. The aim this study was analyze systemic immune characteristics patients We conducted monitor advanced breast cancer undergoing immunotherapy during following course. Peripheral blood mononuclear cells (PBMCs) were collected before after two cycles therapy. Mass cytometry time-of-flight (CyTOF) employed baseline posttreatment cell subpopulations, relationships between proportions these subpopulations occurrence explored. Additionally, we subgroup analyses stratified by anatomic location time onset Furthermore, developed logistic regression predict validated using independent validation cohorts from Gene Expression Omnibus (GEO) database (accession numbers GSE189125 GSE186143). By analyzing 106 samples (n = 16 60 patients), found that high CXCR3+CCR6+CD4+ T CD38+CD86+CXCR3+CCR6+CD8+ low proportion CXCR3lowCD56dim natural killer (NK) at significantly correlated (P 0.0029, P < 0.001, 0.0017, respectively). In analysis, observed consistent results pneumonitis (ir-pneumonitis) thyroiditis (ir-thyroiditis). early irAE group, greater than late group 0.011). An PBMCs revealed thatthe dynamic changes naïve CD4+ NK closely related occurrence. Finally, ultimately irAEs, which yielded an area under receiver operating characteristic curve (AUROC) 0.79 training cohort AUROC 0.75 single-cell (GSE189125). These findings indicate different populations characterization may be used as biomarkers specific toxicities. This will facilitate management lead reduction

Language: Английский

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Advancing Precision Medicine: Uncovering Biomarkers and Strategies to Mitigate Immune-Related Adverse Events in Immune Checkpoint Inhibitors Therapy

Toxicology Reports, Journal Year: 2025, Volume and Issue: unknown, P. 102035 - 102035

Published: April 1, 2025

Language: Английский

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The pathogenesis of neurological immune-related adverse events following immune checkpoint inhibitor therapy

Seminars in Immunology, Journal Year: 2025, Volume and Issue: 78, P. 101956 - 101956

Published: April 27, 2025

Cancer is a leading cause of morbidity and mortality worldwide. The development immune checkpoint inhibitors (ICI) has revolutionised cancer therapy, patients who were previously incurable can now have excellent responses. These therapies work by blocking inhibitory pathways, like cytotoxic T lymphocyte-associated protein 4 (CTLA-4), programmed cell death-1 (PD-1), its ligand PD-L1, lymphocyte activation gene 3 (LAG-3); which leads to increased anti-tumour However, their use lead the immune-related adverse events (irAEs), may result in severe disability, interruption even death. Neurological autoimmune sequelae occur 1-10 % treated with ICIs be fatal. They encompass broad spectrum diseases, affect central peripheral nervous system, include syndromes encephalitis, cerebellitis, neuropathy, myositis. In some cases, neurological irAEs associated autoantibodies recognising neuronal or glial targets. this review, we first describe key targets ICI followed formulation clinical presentations, where focus on syndromes. We comprehensively formulate current literature evaluating surface intracellular autoantibodies, cytokines, chemokines, leukocyte patterns, other blood derived biomarkers, immunogenetic profiles; highlight impact our understanding pathogenesis irAEs. Finally, therapeutic pathways patient outcomes, provide an overview future aspects therapy.

Language: Английский

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Emerging Ocular Side Effects of Immune Checkpoint Inhibitors: A Comprehensive Review

Biomedicines, Journal Year: 2024, Volume and Issue: 12(11), P. 2547 - 2547

Published: Nov. 7, 2024

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, offering significant improvements in patient survival across various malignancies. However, their use is associated with a broad spectrum of immune-related adverse events (irAEs), including those affecting the eye and its surrounding structures, collectively termed ocular irAEs (OirAEs). Although rare, OirAEs (e.g., keratitis, uveitis, retinal vasculitis, etc.) can significantly impact patient's quality life, leading to complications if left untreated. This review provides comprehensive overview ICIs, clinical manifestations, underlying mechanisms, current management strategies. We delve into anterior posterior segment events, highlighting conditions such as dry eye, disorders, well neuro-ophthalmic orbital complications. Furthermore, we discuss challenges diagnosing treating these conditions, particularly given overlap other autoimmune paraneoplastic syndromes. Finally, identify key knowledge gaps suggest future research directions aimed at optimizing while maintaining efficacy therapy. underscores need for increased awareness among clinicians prevent irreversible damage enhance outcomes.

Language: Английский

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Biomarkers in the early stage of PD-1 inhibitor treatment have shown superior predictive capabilities for immune-related thyroid dysfunction

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Oct. 10, 2024

Hematological indicators in the early stage of PD-1 inhibitor treatment may show superior predictive ability occurrence immune related adverse event (irAE) compared to pre-treatment indicators, as response is modulated during treatment. The objective this study was investigate capabilities biomarkers for thyroid dysfunction (irTD), and explore potential cytokines.

Language: Английский

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Development of a predictive model for immune‑related adverse events in patients with cancer

Oncology Letters, Journal Year: 2024, Volume and Issue: 29(3)

Published: Dec. 17, 2024

It is crucial to accurately identify patients with cancer at high risk for immune‑related adverse events (irAEs) caused by immune checkpoint inhibitors (ICIs). The present retrospective study analyzed the factors irAEs in 992 treated ICIs Xi'an International Medical Center Hospital from December 2021 2023. were categorized into one group that experienced (n=276) and a control (n=716) based on occurrence of irAEs. clinical characteristics cancer. Multivariate regression analysis revealed significant differences between two groups terms hypertension, primary cancer, metastasis, targeted drug combination radiotherapy (P<0.05). A nomogram predictive model was developed relevant factors. yielded an area under receiver operating characteristic (ROC) curve 0.672 (95% confidence interval: 0.630‑0.714). In validation set, Hosmer‑Lemeshow goodness‑of‑fit test demonstrated favorable fit chi‑square value 0.787 P‑value 0.978. can effectively high‑risk irAEs, facilitate early identification thereby optimizing management strategies ultimately improving quality life patients.

Language: Английский

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