Association of blood biomarkers and autoimmunity with immune related adverse events in patients with cancer treated with immune checkpoint inhibitors

Scientific Reports, Journal Year: 2021, Volume and Issue: 11(1)

Published: April 27, 2021

Patients with cancer treated immune checkpoint inhibitors (ICIs) develop related adverse events (irAEs), however biomarkers are lacking. We hypothesized that clinicopathologic and laboratory factors would be associated irAE risk overall survival (OS) in this population. In a retrospective study of patients ICIs we collected clinicopathologic, laboratory, irAEs outcomes data. The association between baseline blood biomarkers, features was assessed by logistic regression adjusting for age, sex, smoking, type, performance status, concomitant other systemic therapy, history autoimmune disease (AD), chronic infection pre-existing steroid use (regardless dose). Optimal cutoff values were identified recursive partitioning analysis. 470 identified; 156 (33%) developed irAEs, which absolute lymphocyte count > 2.6 k/ul (adjusted [a]OR: 4.30), monocyte 0.29 (aOR: 2.34) platelet 145 2.23), neutrophil to ratio (NLR) ≤ 5.3 2.07) (MLR) 0.73 2.96), as well 534 5.05). AD 2.57), family 5.98), ICI combination 2.00) had higher odds irAEs. Baseline NLR (aHR: 0.68), MLR 0.43), PLT 0.48) PLR longer OS. history, measurements. Lower NLR, may have favorable prognostic value. Our hypothesis-generating findings require validation larger prospective studies.

Language: Английский

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Uncovering the flip side of immune checkpoint inhibitors: a comprehensive review of immune-related adverse events and predictive biomarkers

International Journal of Biological Sciences, Journal Year: 2024, Volume and Issue: 20(2), P. 621 - 642

Published: Jan. 1, 2024

Immune checkpoint inhibitors (ICIs) have generated considerable excitement as a novel class of immunotherapeutic agents due to their remarkable efficacy in treating various types cancer.However, the widespread use ICIs has brought about number safety concerns, especially development immune-related adverse events (irAEs).These serious complications could result treatment discontinuation and even life-threatening consequences, making it critical identify high-risk groups predictive markers irAEs before initiating therapy.To this end, current article examines several potential important organs affected by ICIs.While retrospective studies yielded some promising results, limitations such small sample sizes, variable patient populations, specific cancer studied make difficult generalize findings.Therefore, prospective cohort real-world investigations are needed validate different biomarkers predicting risk.Overall, identifying is crucial step towards improving enhancing management irAEs.With ongoing research efforts, hoped that more accurate reliable will be identified incorporated into clinical practice guide decisions prevent susceptible patients.

Language: Английский

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Clinical characteristics of rheumatic syndromes associated with checkpoint inhibitors therapy

Lara D. Veeken, Journal Year: 2019, Volume and Issue: 58(Supplement_7), P. vii68 - vii74

Published: June 27, 2019

Abstract Compared with conventional cancer therapies, the spectrum of toxicities observed checkpoint inhibitors is unique and can affect any organ system. Arthralgia myalgia were by far most commonly reported rheumatic immune-related adverse events in clinical trials, there now a growing number case series reports describing features de novo events, which will be focus this review. Some patients develop genuine classic musculoskeletal diseases, but mimic diseases atypical features, mainly polymyalgia rheumatica, rheumatoid arthritis myositis, as well several systemic conditions, including sicca syndrome, vasculitis, sarcoidosis, sclerosis lupus.

Language: Английский

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Rheumatic disorders associated with immune checkpoint inhibitors: what about myositis? An analysis of the WHO’s adverse drug reactions database

Annals of the Rheumatic Diseases, Journal Year: 2020, Volume and Issue: 81(2), P. e32 - e32

Published: Feb. 17, 2020

à la diffusion de documents scientifiques niveau recherche, publiés ou non, émanant des établissements d'enseignement et recherche français étrangers, laboratoires publics privés.

Language: Английский

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Prevalence of Autoimmune Diseases in Patients Treated With Immune Checkpoint Inhibitors: An Epidemiological Study Using A Global Network of Health Care Organizations

ACR Open Rheumatology, Journal Year: 2025, Volume and Issue: 7(1)

Published: Jan. 1, 2025

Objective Evaluate prevalence of new onset autoimmune conditions (ACs) after commencement immune checkpoint inhibitors (ICIs). Methods This retrospective observational study was done using TriNetX. Patients with neoplasm for which ICIs were approved stratified into two groups based on ICI use. Multivariate Cox proportional hazard models and Kaplan Meier method used to assess risk developing ACs among the groups. Subgroup analysis evaluate in patients receiving cytotoxic T‐lymphocyte‐associated protein 4 inhibitor (CTLA4i) versus program cell death 1 (PD1i) ligand (PDL1i) combination treatment (CT) (CTLA4 + PD1i/PDL1i) PD1i/PDL1i. Results who received (2.03% total population) younger (68.7 ± 12.6 vs 71.8 13.9; P < 0.001), predominantly male (54% 41%; 0.0001), White (68% 58%; had lower odds systemic lupus erythematosus (SLE) (0.366% 0.437%, ratio [OR] 0.837; = 0.0005) sclerosis (0.108% 0.135%, OR 0.796; 0.0151), higher rheumatoid arthritis (RA) (2.194% 1.752%, 1.258; 0.0001 1.746; 0.0001). There no significant difference vasculitis, dermatopolymyositis, psoriatic when compared did not receive ICIs. The remained true propensity score matching, except that there SLE (0.37% [n 391] 0.393% n 415], 0.942 [0.82–1.082]; 0.3970). Conclusion have an increased ACs, especially RA. needs be a high index suspicion awareness about prescribers

Language: Английский

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Accelerated atherosclerosis associated with immune checkpoint inhibitors: a systematic review and meta-analysis of pre-clinical studies

Atherosclerosis, Journal Year: 2025, Volume and Issue: unknown, P. 119219 - 119219

Published: May 1, 2025

Language: Английский

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Rheumatic Manifestations and Diseases From Immune Checkpoint Inhibitors in Cancer Immunotherapy

Frontiers in Medicine, Journal Year: 2021, Volume and Issue: 8

Published: Nov. 4, 2021

Immune checkpoint inhibitors (ICIs), which can enhance antitumor immunity and inhibit cancer growth, have revolutionized the treatment of multiple cancers dramatically decreased mortality. However, with ICIs is directly associated immune-related adverse events (irAEs) because inflammation in off-target organs autoimmunity resulting from non-specific immune activation. These irAEs cause rheumatic diseases manifestations such as inflammatory arthritis, polymyalgia rheumatica, myositis, vasculitis, Sicca Sjogen's syndrome, systemic lupus erythematosus. Early diagnosis these will improve outcomes quality life for patients. The induced by requires multidisciplinary cooperation among physicians. Furthermore, underlying mechanisms are not fully understood it difficult to predict evaluate side effects precisely. In this review, we summarize available studies findings about irAEs, focusing mainly on clinical manifestations, epidemiology, possible mechanisms, guiding principles treating irAEs.

Language: Английский

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Construction of an immune-related lncRNA signature pair for predicting oncologic outcomes and the sensitivity of immunosuppressor in treatment of lung adenocarcinoma

Respiratory Research, Journal Year: 2022, Volume and Issue: 23(1)

Published: May 13, 2022

Although immunotherapy has shown clinical activity in lung adenocarcinoma (LUAD), LUAD prognosis been a perplexing problem. We aimed to construct an immune-related lncRNA pairs (IRLPs) score for and identify what immunosuppressor are appropriate which group of people with LUAD.Based on The Cancer Genome Atlas (TCGA)-LUAD cohort, IRLPs were identified scoring system by Cox regression validated the Gene Expression Omnibus (GEO) dataset using log-rank test receiver operating characteristic curve (ROC). Next, we used spearman's correlation analysis, t-test, signaling pathways analysis gene mutation explore immune molecular characteristics different IRLP subgroups. "pRRophetic" package was predict sensitivity immunosuppressant.The constructed based eight calculated as 2.12 × (MIR31HG|RRN3P2) + 0.43 (NKX2-1-AS1|AC083949.1) 1.79 (TMPO-AS1|LPP-AS2) 1.60 (TMPO-AS1|MGC32805) (TMPO-AS1|PINK1-AS) 0.65 (SH3BP5-AS1|LINC01137) 0.51 (LINC01004|SH3PXD2A-AS1) 0.62 (LINC00339|AGAP2-AS1). Patients lower risk had better overall survival (OS) (Log-rank P TCGA train < 0.001, = 0.017, GEO 0.027) similar results observed AUCs (AUC 0.777, AUC 0.685, total 0.733, 0.680). Immune (Cor -0.18893, 0.001), stoma -0.24804, microenvironment -0.22338, 0.001) significantly decreased patients higher score. set enrichment found that high-risk enriched changes DNA chromosomes pathways, this tumor burden (TMB) than low-risk (P 0.0015). Immunosuppressor methotrexate 0.0052), whereas parthenolide rapamycin 0.013) group.Our study established biomarker help prognosis, identification characteristics, patient-tailored selection most suitable therapy.

Language: Английский

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Immune Checkpoint Inhibitor-Associated Scleroderma-Like Syndrome: A Report of a Pembrolizumab-Induced “Eosinophilic Fasciitis-Like” Case and a Review of the Literature

Rheumatology and Therapy, Journal Year: 2020, Volume and Issue: 7(4), P. 1045 - 1052

Published: Oct. 16, 2020

Immune checkpoint inhibitors are a promising new therapeutic strategy in oncology that aims to eliminate cancer cells by enhancing patients' immune response against tumor antigens. Despite their beneficial effects, also responsible for plethora of autoimmune manifestations, known as immune-related adverse events. We present case eosinophilic fasciitis-like disorder an 81-year-old patient treated with the programmed death cell protein 1 inhibitor pembrolizumab non-small-cell lung cancer. The developed characteristic indurated skin lesions his limbs after 1½ years treatment and typical "groove sign." Raynaud's syndrome was absent. A full-thickness biopsy confirmed clinical diagnosis "EF-like" condition. Neither peripheral eosinophilia nor infiltrates were found. His symptoms improved 2.5-month CPI discontinuation 16 mg methylprednisolone slowly tapered dose 4 mg. Eosinophilic fasciitis is rare event treatment; our literature search identified only 12 cases fulfill criteria EF patients receiving CPIs.

Language: Английский

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The Role of Immune Checkpoint Receptors in Regulating Immune Reactivity in Lupus

Cells, Journal Year: 2019, Volume and Issue: 8(10), P. 1213 - 1213

Published: Oct. 8, 2019

Immune checkpoint receptors with co-stimulatory and co-inhibitory signals are important modulators for the immune system. However, unrestricted co-stimulation and/or inadequate co-inhibition may cause breakdown of self-tolerance, leading to autoimmunity. Systemic lupus erythematosus (SLE) is a complex multi-organ disease skewed dysregulated responses interacting genetics environment. The close connections between co-signaling pathways SLE have gradually been established in past research. Also, recent success blockade cancer therapy illustrates importance immunotherapy. Moreover, could result substantial immune-related adverse events that mimic autoimmune diseases, including lupus. Together, regulators represent viable immunotherapeutic targets treatment both autoimmunity cancer. Therefore, it appears reasonable treat by restoring out-of-order axis or manipulating collateral control pathogenic responses. Here, we review current state knowledge regarding relationships T cells, B dendritic neutrophils, highlight their potential clinical implications. Current trials targeting specific axes involved help advance such knowledge, but further in-depth exploration still warranted.

Language: Английский

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