Myocarditis: Etiology, Pathogenesis, and Their Implications in Clinical Practice

Biology, Год журнала: 2023, Номер 12(6), С. 874 - 874

Опубликована: Июнь 17, 2023

Myocarditis is an inflammatory disease of the myocardium caused by infectious or non-infectious agents. It can lead to serious short-term and long-term sequalae, such as sudden cardiac death dilated cardiomyopathy. Due its heterogenous clinical presentation course, challenging diagnosis limited evidence for prognostic stratification, myocarditis poses a great challenge clinicians. As it stands, pathogenesis etiology only partially understood. Moreover, impact certain features on risk assessment, patient outcomes treatment options not entirely clear. Such data, however, are essential in order personalize care implement novel therapeutic strategies. In this review, we discuss possible etiologies myocarditis, outline key processes governing summarize best available regarding state-of-the-art approaches.

Язык: Английский

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PCSK9 Inhibitors in Cancer Patients Treated with Immune-Checkpoint Inhibitors to Reduce Cardiovascular Events: New Frontiers in Cardioncology

Cancers, Год журнала: 2023, Номер 15(5), С. 1397 - 1397

Опубликована: Фев. 22, 2023

Cancer patients treated with immune checkpoint inhibitors (ICIs) are exposed to a high risk of atherosclerosis and cardiometabolic diseases due systemic inflammatory conditions immune-related atheroma destabilization. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is key protein involved in metabolism low-density lipoprotein (LDL) cholesterol. PCSK9 blocking agents clinically available involve monoclonal antibodies, SiRNA reduces LDL levels high-risk atherosclerotic cardiovascular disease events multiple patient cohorts. Moreover, induces peripheral tolerance (inhibition cancer cell- recognition), cardiac mitochondrial metabolism, enhances cell survival. The present review summarizes the potential benefits inhibition through selective antibodies siRNA cancer, especially those ICIs therapies, order reduce potentially improve ICIs-related anticancer functions.

Язык: Английский

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Using Combination therapy to overcome diverse challenges of Immune Checkpoint Inhibitors treatment

International Journal of Biological Sciences, Год журнала: 2024, Номер 20(10), С. 3911 - 3922

Опубликована: Янв. 1, 2024

Immune checkpoint inhibitors (ICIs) have heralded a new era in immunotherapy, representing pivotal breakthrough cancer treatment. Their impact is profound, with ICIs standing as some of the most prescribed anticancer therapies today. Notably, their ability to induce long-term remission even after treatment cessation provides genuine hope for achieving durable cures. However, despite these strides, challenges persist landscape oncology, including resistance phenomena, immune-related adverse events, and suboptimal response rates. In challenges, combination therapy emerges promising approach, poised enhance outcomes address limitations inherent single-agent ICI therapy. By synergistically targeting multiple pathways, holds potential augment therapeutic efficacy while mitigating toxicity impeding emergence mechanisms. Understanding intricacies underlying development events paramount devising novel refined strategies. A timeline showing FDA approvals shown

Язык: Английский

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Cardiovascular toxicity of immune therapies for cancer

BMJ, Год журнала: 2024, Номер unknown, С. e075859 - e075859

Опубликована: Май 15, 2024

In addition to conventional chemoradiation and targeted cancer therapy, the use of immune based therapies, specifically checkpoint inhibitors (ICIs) chimeric antigen receptor T cell therapy (CAR-T), has increased exponentially across a wide spectrum cancers. This been paralleled by recognition off-target related adverse events that can affect almost any organ system including cardiovascular system. The ICIs associated with myocarditis, less common but highly fatal effect, pericarditis pericardial effusions, vasculitis, thromboembolism, potentially accelerated atherosclerosis. CAR-T resulting in systemic cytokine release syndrome myriad consequences arrhythmias, myocardial infarction, heart failure. review summarizes current state knowledge regarding effects CAR-T.

Язык: Английский

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Polymer Nanoparticles for Cancer Immunotherapy: Preparation Methods and Applications

Nature Cell and Science, Год журнала: 2024, Номер 000(000), С. 000 - 000

Опубликована: Июнь 20, 2024

The use of cancer immunotherapy has considerably revolutionized treatment by leveraging the immune system's capacity to specifically target and eliminate malignant cells.However, field still faces several ongoing challenges, including poor tumor invasion, resistance, off-target effects.The targeted administration immunotherapeutics using polymeric nanoparticles (PNPs) been shown increase both efficacy specificity.In this review, we discuss cutting-edge technology PNPs improve effectiveness immunotherapy.This paper summarizes steps in designing developing for delivery modulators, antigens, other bioactive compounds.It also discusses current challenges explores mechanisms which enhance therapeutic outcomes.Tumor microenvironment modifications, immunological activation, prolonged release agents are described, highlighting successes highlighted.

Язык: Английский

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Immune-related cardiovascular toxicities of PD-1/PD-L1 inhibitors in solid tumors: an updated systematic review and meta-analysis

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Янв. 22, 2024

Purpose The objective of this study was to investigate the risk cardiovascular toxicities related PD-1/PD-L1 inhibitors in solid tumors. Methods A literature search performed following participants, interventions, comparisons, outcomes, and design (PICOS) principles, adhered Preferred Reporting Items for Systematic Reviews Meta-Analyses (PRISMA) guidelines. Data analysis conducted using Review Manager version 5.4. Results This meta-analysis included 69 randomized controlled trials (RCTs) divided into five groups based on treatment regimens: + chemotherapy versus chemotherapy, placebo, CTLA-4 chemotherapy. Compared alone, +chemotherapy significantly increased hypertension [all-grade (OR = 1.27, 95% CI [1.05, 1.53], p 0.01); grade 3–5 1.36, [1.04, 1.79], 0.03)], hypotension 2.03, [1.19, 3.45], 0.009); 3.60, [1.22, 10.60], 0.02)], arrhythmia 1.53, [1.02, 2.30], 0.04); 2.91, [1.33, 6.39], 0.008)] myocarditis 2.42, [1.06, 5.54], 0.04)]. all-grade 2.87, [1.26, 6.55], 0.01) [1.13, 3.64], 0.02) when treated with compared placebo. risks are higher PD-1+CTLA-4 PD-1 alone 2.02, [1.12, 3.66], 0.02). Conclusion inhibitor leads an toxicities, especially hypertension, hypotension, arrhythmia, myocarditis.

Язык: Английский

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Cardiovascular Toxicity of Immune Checkpoint Inhibitors: A Guide for Clinicians

Drug Safety, Год журнала: 2023, Номер 46(9), С. 819 - 833

Опубликована: Июнь 21, 2023

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment and care of patients with cancer owing to unique features, including occurrence so-called immune-related adverse events (irAEs). A multidisciplinary team, possibly a cardio-oncology specialist, is warranted achieve favorable patient outcome. Cardiovascular toxicity, especially myocarditis, emerged as life-threatening irAE in real-word setting, European Society Cardiology has recently published first guideline on increase awareness promote standardized approach tackle this complex multimodal issue, diagnostic challenges, assessment, treatment, surveillance receiving ICIs. In article, through question & answer format made up case vignettes, we offer clinically oriented overview latest advancements ICI-related cardiovascular focusing myocarditis associated irAEs (myositis myasthenia gravis within overlap syndrome), purpose assisting clinicians healthcare professionals daily clinical practice.

Язык: Английский

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Gasdermin-E-mediated pyroptosis drives immune checkpoint inhibitor-associated myocarditis via cGAS-STING activation

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Авг. 5, 2024

Immune checkpoint inhibitor (ICI)-induced myocarditis involves intensive immune/inflammation activation; however, its molecular basis is unclear. Here, we show that gasdermin-E (GSDME), a gasdermin family member, drives ICI-induced myocarditis. Pyroptosis mediated by GSDME, but not the canonical GSDMD, activated in myocardial tissue of mice and cancer patients with Deficiency GSDME male alleviates cardiac infiltration T cells, macrophages, monocytes, as well mitochondrial damage inflammation. Restoration expression specifically cardiomyocytes, rather than myeloid GSDME-deficient reproduces Mechanistically, quantitative proteomics reveal GSDME-dependent pyroptosis promotes cell death DNA release, which turn activates cGAS-STING signaling, triggering robust interferon response activation. Pharmacological blockade attenuates improves long-term survival mice. Our findings may advance understanding suggest targeting GSDME-cGAS-STING-interferon axis help prevent manage ICI-associated inflames fatal, mechanism authors identify key driver promoting enhancing our pathogenesis.

Язык: Английский

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Circulating biomarkers in the diagnosis and prognosis of immune checkpoint inhibitor-related myocarditis: time for a risk-based approach

Frontiers in Cardiovascular Medicine, Год журнала: 2024, Номер 11

Опубликована: Фев. 12, 2024

Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that block immune checkpoints and therefore activate cells, allowing them to recognize attack cancer cells. ICIs have revolutionized oncology practice, but their use has been complicated by immune-related adverse events (irAEs). Of cardiovascular (CV) irAEs, ICI-related myocarditis received significant attention due high mortality rates, ranging from 25% 50%, despite its overall low incidence. Establishing the early diagnosis of ICI-myocarditis is important for initiation steroids consideration hospitalization in patients who at risk hemodynamic compromise need acuity care a tertiary setting. In this review, we summarize diagnostic prognostic tools ICI-myocarditis, including electrocardiography, echocardiography, cardiac magnetic resonance imaging, with emphasis on circulating biomarkers. Cardiac troponins (cTns) an essential component provide summary recent studies utilized different assays (cTnI vs. cTnT) outcomes (diagnosis prognosis major outcomes). With exponential increase ICI across indications, there include biomarkers stratification guide treatment. Our review proposes framework future multisite registries, cTn evaluation baseline time irAE suspicion, development central biobanking allow head-to-head clinical validation biomarker ICI-myocarditis. This approach, inclusion CV into pragmatic trials, holds promise improve recognition management thus leading better outcomes.

Язык: Английский

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Cardio-oncology: chances and challenges

Basic Research in Cardiology, Год журнала: 2024, Номер unknown

Опубликована: Сен. 30, 2024

Язык: Английский

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