Cytokine-driven cancer immune evasion mechanisms

International review of cell and molecular biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

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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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Dermatologic toxicities related to cancer immunotherapy

Toxicology Reports, Journal Year: 2025, Volume and Issue: unknown, P. 102021 - 102021

Published: April 1, 2025

Language: Английский

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From ICI to ICU: A systematic review of patients with solid tumors who are treated with immune checkpoint inhibitors (ICI) and admitted to the intensive care unit (ICU)

Cancer Treatment Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 102936 - 102936

Published: April 1, 2025

Immune checkpoint inhibitors (ICIs) have improved the survival of patients with different solid tumors and even resulted in cure metastatic disease. Since introduction ICIs, an increasing number is admitted to ICU for severe potentially life-threatening immune related adverse events (irAEs). The outcome who are because irAEs still unknown. aim this systematic review collect evidence on outcomes irAEs. Medline, Embase, Cochrane central register controlled trials Google Scholar were searched systematically from 1975 24 September 2024. Articles only included when describing after treatment ICIs. Two independent reviewers extracted data assessed risk bias. A total 183 articles included: two prospective population-based studies, four retrospective 25 studies incidental admissions, one case reports, 153 a 177 reports. six contained 169 due In these most frequently reported pneumonitis neurological Of patients, 26% died additional 8% three months thereafter or disease progression. all articles, various described mortality rate varied 0 53%. potential favorable both will probably result more need admissions. Prospective clinical needed optimize strategy at ICU. Based favourable irAEs, admission should definitely be considered

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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Management of immune-related myocarditis, myositis and myasthenia gravis (MMM) overlap syndrome: a single institution case series and literature review

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

Published: May 8, 2025

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of various malignancies, particularly melanoma. However, immune-related adverse events (irAEs) pose significant challenges, in cases severe toxicity syndromes. One such life-threatening irAE is myocarditis, myositis, and myasthenia gravis (MMM) overlap syndrome, which occurs less than 1% patients but has in-hospital mortality rates ranging from 40 to 60%. Due its rarity complexity, early recognition a multidisciplinary approach are critical improving outcomes. We present single-institution case series four diagnosed with MMM syndrome following ICI therapy. Clinical presentation, laboratory findings, imaging, electrophysiological tests were analyzed confirm diagnosis. Therapeutic interventions-including corticosteroids, intravenous immunoglobulins (IVIG), plasma exchange (PLEX), tocilizumab, rituximab- evaluated terms efficacy clinical The onset varied 2 4 weeks after initiating Patients presented rapidly progressive symptoms, including ptosis, bulbar dysfunction, respiratory distress, myopathy, cardiac conduction abnormalities. Immunosuppressive therapy high-dose corticosteroids was initiated all cases. Additional immunomodulatory treatments (IVIG, PLEX, rituximab) administered based on deterioration autoimmune profile. Two achieved complete recovery, one remains maintenance immunosuppression, died due failure despite aggressive treatment. often fatal associated Early identification, immunosuppressive treatment, individualized therapeutic strategies essential optimize patient Further research needed refine diagnostic criteria, identify predictive biomarkers, establish standardized protocols.

Language: Английский

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Development of a lung immune prognostic index-based nomogram model for predicting overall survival and immune-related adverse events in non-small cell lung cancer patients treated with sintilimab

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

Published: May 8, 2025

Sintilimab, a programmed cell death protein-1 (PD-1) inhibitor, has shown efficacy in non-small lung cancer (NSCLC), though response heterogeneity persists. Previous studies suggest that the Lung Immune Prognostic Index (LIPI) may predict prognosis and immune-related adverse events (irAEs) immunotherapy. This study aimed to develop validate LIPI-based nomograms for predicting overall survival (OS) irAEs NSCLC patients treated with sintilimab. Multicenter data stratified 356 into training, internal validation, external validation cohorts. Propensity score matching (PSM) balanced baseline characteristics. Multivariable Cox regression identified OS predictors, were constructed using significant variables. Model performance was evaluated via concordance index (C-index), time-dependent receiver operating characteristic (ROC) curves, calibration plots, decision curve analysis (DCA). Kaplan-Meier assessed risk stratification. Independent prognostic factors include clinical stage, treatment lines, LIPI scores albumin level. Among them, stage IV (hazard ratio [HR]=1.725, 95% confidence interval [CI] 1.529-1.902), line ≥2 (HR=1.302, 95%CI: 1.125-1.569), intermediate (HR=1.736, 1.586-1.925), poor (HR=1.568, CI: 1.361-1.637) level≥35 (HR=1.802, 1.698-2.023) OS. The prediction model demonstrated excellent discrimination across all cohorts, AUCs maintaining 0.770-0.850 1-2 year predictions. Consistent observed (C-index: training=0.778, validation=0.793, validation=0.790). For prediction, predictors included age, sex, Eastern Cooperative Oncology Group status (ECOG PS), scores. Similarly, showed robust (AUCs 0.754-0.835 predictions; C-index: training=0.805, validation=0.825, validation=0.775). Both significantly outperformed single-variable predictions analyses. DCA confirmed superior net benefit. effectively predicted sintilimab-treated patients, offering valuable tools personalized decision-making.

Language: Английский

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Immune checkpoint inhibitor (ICI) therapy in central nervous system cancers: State-of-the-art and future outlook

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 159, P. 114837 - 114837

Published: May 19, 2025

Language: Английский

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Single-cell RNA sequencing of baseline PBMCs predicts ICI efficacy and irAE severity in patients with NSCLC

Journal for ImmunoTherapy of Cancer, Journal Year: 2025, Volume and Issue: 13(5), P. e011636 - e011636

Published: May 1, 2025

Background Immune checkpoint inhibitors (ICIs) have transformed treatment and provided significant clinical benefits durable responses for patients with advanced non-small cell lung cancer (NSCLC). However, only a small percentage of respond to ICI treatment, immune-related adverse events (irAEs) leading discontinuation remain challenging. Despite the recognized need biomarkers predict both efficacy ICIs risk irAEs, such are yet be clearly identified. Methods In this study, we performed single-cell RNA sequencing (scRNA-seq) peripheral blood mononuclear cells (PBMCs) from 33 NSCLC before treatment. To validate our findings, reanalyzed public scRNA-seq data, conducted cytometric bead array (CBA), supported findings T-cell receptor sequencing. Results While immune response was more pronounced in favorable prognosis, hypoxic pathway prominent primary resistance. Lymphocytes as CD8 T cells, CD4 natural killer were primarily involved these pathways, PRF1 GZMB expression showing strong associations prognosis. contrast, irAEs mainly linked myeloid monocytes macrophages. As irAE severity increased, inflammation TNF-NFKB1 prominent. Specifically, increased IL1B , CXCL8 CXCL2 TNF macrophages closely associated severe through involvement pathways. Notably, increase showed close association prognosis reduced irAE, which validated CBA analysis. Moreover, key markers varied according regardless patient background, programmed death-ligand 1 levels, tumor histology, or prior regimens. Conclusions This study identified biological pathways using PBMC samples These provide foundation improved therapeutic strategies that enhance outcomes while minimizing treatment-associated risks.

Language: Английский

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