Immune-related adverse events of immune checkpoint inhibitors: a review

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Май 25, 2023

Since the first Immune Checkpoint Inhibitor was developed, tumor immunotherapy has entered a new era, and response rate survival of many cancers have also been improved. Despite success immune checkpoint inhibitors, resistance limits number patients who can achieve lasting response, immune-related adverse events complicate treatment. The mechanism (irAEs) is unclear. We summarize discuss mechanisms action different types their possible mechanisms, describe strategies targets for prevention therapeutic interventions to mitigate them.

Язык: Английский

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Drug-Induced Hypersensitivity Syndrome (DIHS)/Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS): Clinical Features and Pathogenesis

The Journal of Allergy and Clinical Immunology In Practice, Год журнала: 2022, Номер 10(5), С. 1155 - 1167.e5

Опубликована: Фев. 15, 2022

Язык: Английский

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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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Immune-Related Adverse Events Due to Cancer Immunotherapy: Immune Mechanisms and Clinical Manifestations

Cancers, Год журнала: 2024, Номер 16(7), С. 1440 - 1440

Опубликована: Апрель 8, 2024

The landscape of cancer treatment has undergone a significant transformation with the introduction Immune Checkpoint Inhibitors (ICIs). Patients undergoing these treatments often report prolonged clinical and radiological responses, albeit potential risk developing immune-related adverse events (irAEs). Here, we reviewed discussed mechanisms action ICIs their pivotal role in regulating immune system to enhance anti-tumor response. We scrutinized intricate pathogenic responsible for irAEs, arising from evasion self-tolerance checkpoints due drug-induced modulation. also summarized main manifestations irAEs categorized by organ types, detailing incidence associated factors. occurrence is more frequent when are combined; neurological, cardiovascular, hematological, rheumatic commonly linked PD1/PD-L1 inhibitors cutaneous gastrointestinal prevalent CTLA4 inhibitors. Due often-nonspecific signs symptoms, diagnosis (especially those rare ones) can be challenging. differential primary autoimmune disorders becomes sometimes intricate, given pathophysiological similarities. In conclusion, considering escalating use ICIs, this area research necessitates additional studies practical insights, especially development biomarkers predicting toxicities. addition, there need heightened education both clinicians patients understanding awareness.

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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Drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms. Part I. Epidemiology, pathogenesis, clinicopathological features, and prognosis

Journal of the American Academy of Dermatology, Год журнала: 2023, Номер 90(5), С. 885 - 908

Опубликована: Июль 28, 2023

Язык: Английский

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Molecular Mechanisms of Cutaneous Immune-Related Adverse Events (irAEs) Induced by Immune Checkpoint Inhibitors

Current Oncology, Год журнала: 2023, Номер 30(7), С. 6805 - 6819

Опубликована: Июль 18, 2023

Over the past few decades, immune checkpoint inhibitors (ICIs) have emerged as promising therapeutic options for treatment of various cancers. These novel treatments effectively target key mediators pathways. Currently, ICIs primarily consist monoclonal antibodies that specifically block cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death 1 (PD-1), death-ligand (PD-L1), and lymphocyte activation gene 3 protein (LAG-3). Despite notable efficacy in cancer treatment, they can also trigger immune-related adverse events (irAEs), which present autoimmune-like or inflammatory conditions. IrAEs potential to affect multiple organ systems, with cutaneous toxicities being most commonly observed. Although irAEs are typically low-grade severity usually be managed effectively, there cases where severe become life-threatening. Therefore, early recognition a comprehensive understanding mechanisms underlying crucial improving clinical outcomes patients. However, precise pathogenesis remains unclear. This review focuses on skin manifestations induced by ICIs, prognosis related irAEs, exploration involved irAEs.

Язык: Английский

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Toxicity in the era of immune checkpoint inhibitor therapy

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Авг. 23, 2024

Immune checkpoint inhibitors (ICIs) reinvigorate anti-tumor immune responses by disrupting co-inhibitory molecules such as programmed cell death 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4). Although ICIs have had unprecedented success become the standard of care for many cancers, they are often accompanied off-target inflammation that can occur in any organ system. These related adverse events (irAEs) require steroid use and/or cessation ICI therapy, which both lead to cancer progression. irAEs common, detailed molecular mechanisms underlying their development still elusive. To further our understanding develop effective treatment options, there is pressing need preclinical models recapitulating clinical settings. In this review, we describe current implications ICI-induced skin toxicities, colitis, neurological endocrine pneumonitis, arthritis, myocarditis along with management.

Язык: Английский

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Incidence of Cutaneous Immune-Related Adverse Events and Outcomes in Immune Checkpoint Inhibitor-Containing Regimens: A Systematic Review and Meta-Analysis

Cancers, Год журнала: 2024, Номер 16(2), С. 340 - 340

Опубликована: Янв. 13, 2024

Immune checkpoint inhibitors (ICIs) are used to treat many cancers, and cutaneous immune-related adverse events (cirAEs) among the most frequently encountered toxic effects. Understanding incidence prognostic associations of cirAEs is importance as their uses in different settings, combinations, tumor types expand. To evaluate association with outcome measures across a variety ICI regimens we performed systematic review meta-analysis published trials anti-programmed death-1/ligand-1 (PD-1/PD-L1) anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) ICIs, both alone combination chemotherapy, antiangiogenic agents, or other ICIs patients melanoma, renal cell carcinoma, non-small lung cancer, urothelial carcinoma. Key findings our study include variable cirAE tumors regimens, positive increased response rate, well significant between vitiligo overall survival. Across 174 studies, rash, pruritis, were reported cirAEs, incidences 16.7%, 18.0%, 6.6%, respectively. Higher was associated CTLA-4-containing particularly higher doses ipilimumab, compared PD-1/L1 monotherapies. Outcome including rate progression-free survival positively correlated cirAEs. The vitiligo, rash expected rises 0.17% (

Язык: Английский

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Cutaneous Adverse Events and Cancer Survival Prognosis With Immune Checkpoint Inhibitor Treatment

JAMA Dermatology, Год журнала: 2023, Номер 159(10), С. 1093 - 1093

Опубликована: Сен. 6, 2023

Growing research suggests that the prevalence of cutaneous immune-related adverse events (cirAEs) is associated with favorable outcomes among individuals cancer who receive immune checkpoint inhibitor (ICI) treatment.

Язык: Английский

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