Cardiotoxicity of immune checkpoint inhibitors
Gilda Varricchi,Maria Rosaria Galdiero,Giancarlo Marone,Gjada Criscuolo,Maria Triassi,Domenico Bonaduce,Gianni Marone,Carlo G. Tocchetti +7 more
- Vol. 2, Iss: 4
TLDR
The mechanisms of the most prominent checkpoint inhibitors are described, specifically ipilimumab (anti-CTLA-4, the godfather of checkpoint inhibitors) patient and monoclonal antibodies targeting PD-1 and PD-L1 (eg, atezolizumab).Abstract:
Cardiac toxicity after conventional antineoplastic drugs (eg, anthracyclines) has historically been a relevant issue. In addition, targeted therapies and biological molecules can also induce cardiotoxicity. Immune checkpoint inhibitors are a novel class of anticancer drugs, distinct from targeted or tumour type-specific therapies. Cancer immunotherapy with immune checkpoint blockers (ie, monoclonal antibodies targeting cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), programmed cell death 1 (PD-1) and its ligand (PD-L1)) has revolutionised the management of a wide variety of malignancies endowed with poor prognosis. These inhibitors unleash antitumour immunity, mediate cancer regression and improve the survival in a percentage of patients with different types of malignancies, but can also produce a wide spectrum of immune-related adverse events. Interestingly, PD-1 and PD-L1 are expressed in rodent and human cardiomyocytes, and early animal studies have demonstrated that CTLA-4 and PD-1 deletion can cause autoimmune myocarditis. Cardiac toxicity has largely been underestimated in recent reviews of toxicity of checkpoint inhibitors, but during the last years several cases of myocarditis and fatal heart failure have been reported in patients treated with checkpoint inhibitors alone and in combination. Here we describe the mechanisms of the most prominent checkpoint inhibitors, specifically ipilimumab (anti-CTLA-4, the godfather of checkpoint inhibitors) patient and monoclonal antibodies targeting PD-1 (eg, nivolumab, pembrolizumab) and PD-L1 (eg, atezolizumab). We also discuss what is known and what needs to be done about cardiotoxicity of checkpoint inhibitors in patients with cancer. Severe cardiovascular effects associated with checkpoint blockade introduce important issues for oncologists, cardiologists and immunologists.read more
Citations
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Diretriz Brasileira de Cardio-oncologia - 2020
Ludhmila Abrahão Hajjar,Isabela Bispo Santos da Silva Costa,Marcelo Antônio Cartaxo Queiroga Lopes,Paulo M. Hoff,Maria Del Pilar Estevez Diz,Silvia Moulin Ribeiro Fonseca,Cristina Salvadori Bittar,Marilia Harumi Higuchi dos Santos Rehder,Stephanie Itala Rizk,Dirceu R. Almeida,Gustavo Spadaccia dos Santos Fernandes,Luís Beck-da-Silva,Carlos M. Campos,Marcelo Westerlund Montera,Silvia Marinho Martins Alves,Julia Tizue Fukushima,Maria Veronica Camara dos Santos,Carlos Eduardo Negrão,Thiago Liguori Feliciano da Silva,Silvia Moreira Ayub Ferreira,Marcus Vinícius Bolívar Malachias,Maria da Consolação Vieira Moreira,Manuel Maria Ramos Valente Neto,Veronica Cristina Quiroga Fonseca,Maria Carolina Feres de Almeida Soeiro,Juliana Barbosa Sobral Alves,Carolina Maria Pinto Domingues Carvalho Silva,João C.N. Sbano,Ricardo Pavanello,Ibraim Pinto,Antonio Felipe Simão,Marianna Deway Andrade Dracoulakis,Ana O. Hoff,Bruna Morhy Borges Leal Assunção,Yana Novis,Laura Testa,Aristóteles Comte de Alencar Filho,Cecilia Cruz,Juliana Pereira,Diego Ribeiro Garcia,Cesar Higa Nomura,Carlos E. Rochitte,Ariane Vieira Scarlatelli Macedo,Patricia Tavares Felipe Marcatti,Wilson Mathias Junior,Evanius Garcia Wiermann,Renata do Val,Helano Freitas,Anelisa Coutinho,Clarissa Maria de Cerqueira Mathias,Fernando Meton de Alencar Camara Vieira,Andre Deeke Sasse,Vanderson Rocha,José Antonio Franchini Ramires,Roberto Kalil Filho +54 more
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Susceptible loci associated with autoimmune disease as potential biomarkers for checkpoint inhibitor-induced immune-related adverse events.
TL;DR: This review extensively searched for susceptible loci associated with various autoimmune diseases, and pooled them in groups most likely to be associated with CPI-induced irAEs, to help guide physicians in a more refined and personal manner.
Journal ArticleDOI
Management of Cardiac Toxicity Induced by Chemotherapy.
Dario Trapani,Paola Zagami,Paola Zagami,Eleonora Nicolò,Eleonora Nicolò,Gabriella Pravettoni,Gabriella Pravettoni,Giuseppe Curigliano,Giuseppe Curigliano +8 more
TL;DR: This present review aimed to provide a perspective and an update of the current pharmacotherapy approaches for the prevention and management of cardiotoxicity from antiblastic chemotherapy, by navigating the current knowledge and clinical indications in support of the medical interventions.
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BRD4 inhibition suppresses PD-L1 expression in triple-negative breast cancer.
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Cardiac toxicity of immune-checkpoint inhibitors: a clinical case of nivolumab-induced myocarditis and review of the evidence and new challenges
Roberto Martin Huertas,Cristina Saavedra Serrano,Cristian Perna,Ana Ferrer Gómez,Teresa Alonso Gordoa +4 more
TL;DR: A clinical case of a patient with advanced kidney cancer treated with nivolumab as a third line treatment, who died and a necropsy study was performed, identifying a set of clinical, analytical and electrocardiographic alterations compatible with myocarditis.
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