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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Anti-cancer immunotherapy-related cardiotoxicity: preventable and treatable

Visualized Cancer Medicine, Год журнала: 2025, Номер 6, С. 1 - 1

Опубликована: Янв. 1, 2025

Anti-cancer immunotherapies, particularly immune checkpoint inhibitors, have significantly advanced oncology treatments but are associated with rare, potentially severe cardiotoxicities. Despite their success, these therapies immune-related adverse events including rare immunotherapy-related This review examines various immunotherapy types, such as adoptive T-cell therapies, and cancer vaccines, highlighting cardiovascular risks. Cardiotoxicities can lead to life-threatening complications, especially in high-risk patients. Early detection prevention crucial, comprehensive assessments routine biomarker monitoring playing a central role. With immunotherapies becoming more prevalent, this calls for stronger evidence-based guidelines manage prevent ensuring that patients benefit from life-saving without jeopardizing health.

Язык: Английский

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Cardiogenic shock in patients with active onco-hematological malignancies: A multicenter retrospective study

Journal of Critical Care, Год журнала: 2025, Номер 87, С. 155028 - 155028

Опубликована: Янв. 22, 2025

Язык: Английский

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Advancements in Diagnosis and Treatment of Cardiac Sarcomas: A Comprehensive Review

Current Treatment Options in Oncology, Год журнала: 2025, Номер 26(2), С. 103 - 127

Опубликована: Янв. 31, 2025

Язык: Английский

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Efficacy of high-dose steroids versus low-dose steroids in the treatment of immune checkpoint inhibitor-associated myocarditis: a case series and systematic review

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Фев. 12, 2025

Immune checkpoint inhibitor-associated myocarditis (ICI-M) is a rare yet potentially fatal complication of immunotherapy, with no standardized treatment protocol due to limited data. The use varying steroid doses has resulted in inconsistent outcomes. We retrospectively identified patients diagnosed ICI-M at our institution between January 2020 and February 2024. Additionally, we conducted comprehensive literature review using PubMed, Embase, the Cochrane Library facilitate comparative analysis clinical responses. primary aim was compare outcomes therapeutic responses treated high-dose versus low-dose methylprednisolone. Patients receiving an initial intravenous methylprednisolone (1 g/day) exhibited more rapid reduction myocardial injury markers, including troponin I/T (cTnI/T), creatine kinase (CK), N-terminal pro b-type natriuretic peptide (NT-proBNP), compared those lower doses. This group also demonstrated incidences biomarker rebound maintained levels over time. process straightforward group, efficacy surpassing that observed who received (mPSL) dose less than 1 g/day. Regarding prognosis, incidence major adverse cardiovascular events (MACE) mortality significantly group. In immune myocarditis, prompt administration corticosteroid pulse therapy strongly associated improved intervention rapidly lowers biomarkers (cTnI/T, CK, NT-proBNP) while minimizing risk rebound, thus optimizing management. Notably, it reduces (MACE), thereby enhancing patient prognosis. duration should be tailored based on response. cases resistance, combination therapies may provide additional benefit.

Язык: Английский

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Preoperative inflammatory markers and tumor markers in predicting lymphatic metastasis and postoperative complications in colorectal cancer: a retrospective study

BMC Surgery, Год журнала: 2025, Номер 25(1)

Опубликована: Фев. 18, 2025

To analyze the impact of preoperative inflammatory markers and tumor on lymphatic metastasis postoperative complications in colorectal cancer patients, explore their predictive value for these outcomes. Furthermore, based marker indicators with significant effects, models risk incidence will be constructed. This study retrospectively analyzed clinical data CRC patients who underwent surgical treatment at Shanxi Bethune Hospital between January 2021 June 2024. Preoperative were compared lymph node-positive node-negative groups. Variables selected using Lasso regression, independent factors influencing node identified through multivariate logistic regression analysis. Based results, a Nomogram prediction model was constructed, its accuracy evaluated calibration curve. The discriminatory ability assessed ROC curve, applicability DCA Similarly, predicting complications, Pearson correlation analysis used to examine relationships markers, complications. curves employed calculate AUC optimal cutoff values each marker. Kaplan-Meier (KM) DFS. Independent univariate analyses, constructed validated. A total 196 included study. NLR, PLR, FAR, CEA, CA199, CA724 levels significantly elevated group (P < 0.05). smoking history, as non-zero coefficient variables. Multivariate further confirmed history (HR = 4.20), NLR 2.52), FAR 1.18), 1.32) predictors results showed high accuracy, curve 0.880, indicating excellent ability. decision demonstrated good applicability. In complication prediction, revealed positive rates 0.05), coefficients 0.24, 0.34, 0.16, 0.19, respectively, PLR showing strongest correlation. that AUCs LMR, CAR 0.633, 0.675, 0.467, 0.580, 0.559, 4.29, 261.71, 3.39, 18.20, 11.26, respectively. 0.567, 0.612, 0.609, 11.87, 10.27, 6.85. KM higher CAR, associated poorer Univariate 1.53) 1.11) indicated 0.729, demonstrating ability, have occurrence certain developed this provide reference personalized diagnosis treatment, but practical application needs validated large-scale studies.

Язык: Английский

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Microbiota-indole-3-propionic acid-heart axis mediates the protection of leflunomide against αPD1-induced cardiotoxicity in mice

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Март 19, 2025

Anti-programmed death 1 (αPD1) immune checkpoint blockade is used in combination for cancer treatment but associated with cardiovascular toxicity. Leflunomide (Lef) can suppress the growth of several tumor and mitigate cardiac remodeling mice. However, role Lef αPD1-induced cardiotoxicity remains unclear. Here, we report that inhibits αPD1-related without compromising efficacy αPD1-mediated immunotherapy. changes community structure gut microbiota αPD1-treated melanoma-bearing Moreover, mice receiving transplants from Lef+αPD1-treated have better function compared to Mechanistically, analyze metabolomics identify indole-3-propionic acid (IPA), which protects dysfunction IPA directly bind aryl hydrocarbon receptor promote phosphoinositide 3-kinase expression, thus curtailing cardiomyocyte response injury. Our findings reveal mitigates toxicity through modulation microbiota-IPA-heart axis. The authors show leflunomide microbiota-indole-3-propionic acid-heart

Язык: Английский

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Immune Checkpoint Inhibitors and Cardiovascular Adverse Events

ESC Heart Failure, Год журнала: 2025, Номер unknown

Опубликована: Апрель 10, 2025

Abstract In the last years, we assisted to a tremendous increase in therapeutic options for management of cancers, with immunotherapy at forefront this innovation. Immune checkpoint inhibitors (ICIs) have been developed enhance activity immune system against cancer cells (1) and number approvals ICIs has rapidly increased. also associated disinhibited cytotoxic T that damage healthy tissue multiple organs, causing immune‐related adverse events (AEs). Cardiovascular AEs (CVAe) are increasingly reported: myocarditis, Takotsubo syndrome, pericarditis pericardial effusion, worsening atherosclerosis, acute coronary syndromes, non‐inflammatory heart failure, ischaemic stroke. They classified into five grades, based on presenting symptoms, level cardiac biomarkers, imaging. Even though myocarditis occurs more frequently than previously thought, clinically relevant is rare irAE compared other (0.5–1.2%). The clinical manifestations range from mild symptoms such as chest pain, cardiogenic shock. prognosis severe, mortality rates ranging 25% 50%. It concomitant use combination inhibitors. treatment strategies tripartite: (i) holding ICI prevent further toxicity, (ii) immunosuppression alleviate inflammatory changes, (iii) supportive therapy address complications. Glucocorticoids represent first‐line treatment. hemodynamically unstable patients, high‐dose steroids should be initiated (intravenous methylprednisolone 1000 or 1250 mg oral during 4 days). ICI‐associated can accompanied by no/mild effusion up tamponade. made nonsteroidal anti‐inflammatory drugs colchicine, corticosteroids if needed, pericardiocentesis large effusions. could continued Grade 1 pericarditis, while temporary suspension warranted severe cases. There significant potential accelerated atherosclerosis long‐term effect, but atherosclerosis‐related CVAEs not frequent, especially treatment; increasing evidence associates progression increased atherosclerotic cardiovascular disease. lead arrhythmias: atrial fibrillation, supraventricular ventricular tachycardias. Non‐inflammatory failure syndrome observed ICI‐treated patients. seem involved development right dysfunction pulmonary arterial hypertension. outmost importance improve collaboration among different medical figures, cardiologists, oncologists, endocrinologists, immunologists, both practice basic science research, better recognize these events, understand their pathophysiological mechanisms, overall survival quality life affected

Язык: Английский

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Treatment of unresectable stage III non-small cell lung cancer for patients who are under-represented in clinical trials

Cancer Treatment Reviews, Год журнала: 2024, Номер 129, С. 102797 - 102797

Опубликована: Июль 3, 2024

Язык: Английский

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Blocking CTLA‐4 promotes pressure overload‐induced heart failure via activating Th17 cells

The FASEB Journal, Год журнала: 2024, Номер 38(15)

Опубликована: Авг. 7, 2024

Abstract Targeting cytotoxic T‐lymphocyte‐associated antigen‐4 (CTLA‐4) with specific antibody offers long‐term benefits for cancer immunotherapy but can cause severe adverse effects in the heart. This study aimed to investigate role of anti‐CTLA‐4 pressure overload‐induced cardiac remodeling and dysfunction. Transverse aortic constriction (TAC) was used induce hypertrophy heart failure mice. Two weeks after TAC treatment, mice received injection twice a week at dose 10 mg/kg body weight. The administration exacerbated TAC‐induced decline function, intensifying myocardial fibrosis. Further investigation revealed that significantly elevated systemic inflammatory factors levels facilitated differentiation T helper 17 (Th17) cells peripheral blood TAC‐treated Importantly, mediated Th17 hypertrophic phenotype were dramatically alleviated by inhibition interleukin‐17A (IL‐17A) an anti‐IL‐17A antibody. Furthermore, C‐X‐C motif chemokine receptor 4 (CXCR4) antagonist AMD3100, also reversed anti‐CTLA‐4‐mediated cardiotoxicity Overall, these results suggest exacerbates activating promoting cells. CXCR4/Th17/IL‐17A axis could be potential therapeutic strategy mitigating immune checkpoint inhibitors‐induced cardiotoxicity.

Язык: Английский

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