{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T08:24:06Z","timestamp":1784795046955,"version":"3.55.0"},"reference-count":111,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T00:00:00Z","timestamp":1708473600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health [Ricerca corrente]"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In recent years, immune checkpoint inhibitors have significantly changed the field of oncology, emerging as first-line treatment, either alone or in combination with other regimens, for numerous malignancies, improving overall survival and progression-free survival in these patients. However, immune checkpoint inhibitors might also cause severe or fatal immune-related adverse events, including adverse cardiovascular events. Initially, myocarditis was recognized as the main immune checkpoint inhibitor-related cardiac event, but our knowledge of other potential immune-related cardiovascular adverse events continues to broaden. Recently, preclinical and clinical data seem to support an association between immune checkpoint inhibitors and accelerated atherosclerosis as well as atherosclerotic cardiovascular events such as cardiac ischemic disease, stroke, and peripheral artery disease. In this review, by offering a comprehensive overview of the pivotal role of inflammation in atherosclerosis, we focus on the potential molecular pathways underlying the effects of immune checkpoint inhibitors on cardiovascular diseases. Moreover, we provide an overview of therapeutic strategies for cancer patients undergoing immunotherapy to prevent the development of cardiovascular diseases.<\/jats:p>","DOI":"10.3390\/ijms25052502","type":"journal-article","created":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T04:23:10Z","timestamp":1708489390000},"page":"2502","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Association between Immune Checkpoint Inhibitors and Atherosclerotic Cardiovascular Disease Risk: Another Brick in the Wall"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-3409-5482","authenticated-orcid":false,"given":"Linda","family":"Piras","sequence":"first","affiliation":[{"name":"Department of Clinical and Molecular Medicine, Sapienza University of Rome, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Zuccanti","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Medicine, Sapienza University of Rome, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Russo","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Medicine, Sapienza University of Rome, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Riccio","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Medicine, Sapienza University of Rome, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0080-7309","authenticated-orcid":false,"given":"Antonio","family":"Agresti","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Medicine, Sapienza University of Rome, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Lustri","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Medicine, Sapienza University of Rome, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"Dardani","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Medicine, Sapienza University of Rome, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7291-2450","authenticated-orcid":false,"given":"Armando","family":"Ferrera","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Medicine, Sapienza University of Rome, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Fiorentini","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Medicine, Sapienza University of Rome, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0635-4921","authenticated-orcid":false,"given":"Giuliano","family":"Tocci","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Medicine, Sapienza University of Rome, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Tini Melato","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Medicine, Sapienza University of Rome, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Volpe","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Medicine, Sapienza University of Rome, 00189 Rome, Italy"},{"name":"IRCCS San Raffaele, 00166 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele","family":"Barbato","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Medicine, Sapienza University of Rome, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9195-5977","authenticated-orcid":false,"given":"Allegra","family":"Battistoni","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Medicine, Sapienza University of Rome, 00189 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.jaccao.2020.11.012","article-title":"The Evolving Immunotherapy Landscape and the Epidemiology, Diagnosis, and Management of Cardiotoxicity","volume":"3","author":"Zhang","year":"2021","journal-title":"JACC CardioOncology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1126\/science.aar4060","article-title":"Cancer immunotherapy using checkpoint blockade","volume":"359","author":"Ribas","year":"2018","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/j.jacc.2021.11.048","article-title":"Immune Checkpoint Therapies and Atherosclerosis: Mechanisms and Clinical Implications","volume":"79","author":"Vuong","year":"2022","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1056\/NEJMra1703481","article-title":"Immune_related adverse events associated with immune checkpoint blockade","volume":"378","author":"Postow","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1016\/S0140-6736(18)30533-6","article-title":"Increased reporting of fatal immune checkpoint inhibitor-associated myocar_ditis","volume":"391","author":"Moslehi","year":"2018","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3430","DOI":"10.1200\/JCO.21.01808","article-title":"Incidence of cardiovascular events in patients treated with immune checkpoint inhibitors","volume":"40","author":"Laenens","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1016\/j.jacc.2018.02.037","article-title":"Myocarditis in Patients Treated With Immune Checkpoint Inhibitors","volume":"71","author":"Mahmood","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1161\/CIRCULATIONAHA.119.044703","article-title":"Major Adverse Cardiovascular Events and the Timing and Dose of Corticosteroids in Immune Checkpoint Inhibitor\u2013Associated Myocarditis","volume":"141","author":"Zhang","year":"2020","journal-title":"Circ."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"S8","DOI":"10.21037\/tlcr.2017.12.10","article-title":"Evaluation of rare but severe immune related adverse effects in PD-1 and PD-L1 inhibitors in non\u2013small cell lung cancer: A meta-analysis","volume":"6","author":"Hu","year":"2017","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s40425-016-0152-y","article-title":"Cardiotoxicity associated with CTLA4 and PD1 blocking immunotherapy","volume":"4","author":"Heinzerling","year":"2016","journal-title":"J. Immunother. Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1056\/NEJMoa1707914","article-title":"Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease","volume":"377","author":"Ridker","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2497","DOI":"10.1056\/NEJMoa1912388","article-title":"Efficacy and safety of low-dose colchicine after myocardial infarction","volume":"381","author":"Tardif","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.jacc.2012.10.027","article-title":"Low-Dose Colchicine for Secondary Prevention of Cardiovascular Disease","volume":"61","author":"Nidorf","year":"2013","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1852","DOI":"10.1161\/CIRCRESAHA.114.302721","article-title":"Mechanisms of Plaque Formation and Rupture","volume":"114","author":"Bentzon","year":"2014","journal-title":"Circ. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1161\/ATVBAHA.112.300173","article-title":"Phenotypic Polarization of Macrophages in Atherosclerosis","volume":"33","author":"Leitinger","year":"2013","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1056\/NEJM199901143400207","article-title":"Atherosclerosis as an inflammatory disease","volume":"340","author":"Ross","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/s41392-022-00955-7","article-title":"Inflammation and atherosclerosis: Signaling pathways and therapeutic intervention","volume":"7","author":"Kong","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2752","DOI":"10.1172\/JCI119465","article-title":"IFN-gamma potentiates atherosclerosis in ApoE knock-out mice","volume":"99","author":"Gupta","year":"1997","journal-title":"J. Clin. Investig."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1161\/01.ATV.0000143933.20616.1b","article-title":"Inhibition of Tumor Necrosis Factor-\u03b1 Reduces Atherosclerosis in Apolipoprotein E Knockout Mice","volume":"24","author":"Hovgaard","year":"2004","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.cardiores.2005.01.001","article-title":"Tumor necrosis factor-? promotes atherosclerotic lesion progression in APOE*3-leiden transgenic mice","volume":"66","author":"Boesten","year":"2005","journal-title":"Cardiovasc. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1161\/CIRCRESAHA.107.155838","article-title":"Targeting Interferon-\u03b3 to Treat Atherosclerosis","volume":"101","author":"Gotsman","year":"2007","journal-title":"Circ. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1161\/01.CIR.104.2.197","article-title":"In Vivo Downregulation of T Helper Cell 1 Immune Responses Reduces Atherogenesis in Apolipoprotein E-Knockout Mice","volume":"104","author":"Laurat","year":"2001","journal-title":"Circulation"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1172\/JCI18607","article-title":"Disruption of TGF-\u03b2 signaling in T cells accelerates atherosclerosis","volume":"112","author":"Robertson","year":"2003","journal-title":"J. Clin. Investig."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1194\/jlr.D000497","article-title":"The role of CD4+CD25+ regulatory T cells in macrophage-derived foam-cell formation","volume":"51","author":"Lin","year":"2010","journal-title":"J. Lipid Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e17","DOI":"10.1161\/01.RES.85.8.e17","article-title":"Protective Role of Interleukin-10 in Atherosclerosis","volume":"85","author":"Mallat","year":"1999","journal-title":"Circ. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1161\/01.ATV.0000114567.76772.33","article-title":"Transforming Growth Factor \u03b2 and Atherosclerosis: So Far, So Good for the Protective Cytokine Hypothesis","volume":"24","author":"Grainger","year":"2004","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1038\/nm1343","article-title":"Natural regulatory T cells control the development of atherosclerosis in mice","volume":"12","author":"Salomon","year":"2006","journal-title":"Nat. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.atherosclerosis.2013.06.014","article-title":"Decreased numbers of regulatory T cells are associated with human atherosclerotic lesion vulnerability and inversely correlate with infiltrated mature dendritic cells","volume":"230","author":"Dietel","year":"2013","journal-title":"Atherosclerosis"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1172\/JCI200420479","article-title":"IL-5 links adaptive and natural immunity specific for epitopes of oxidized LDL and protects from atherosclerosis","volume":"114","author":"Binder","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1161\/CIRCRESAHA.115.306427","article-title":"Adaptive Response of T and B Cells in Atherosclerosis","volume":"118","author":"Ketelhuth","year":"2016","journal-title":"Circ. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1161\/hq0302.104905","article-title":"Interleukin-4 Deficiency Decreases Atherosclerotic Lesion Formation in a Site-Specific Manner in Female LDL Receptor\u2212\/\u2212 Mice","volume":"22","author":"King","year":"2002","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1161\/CIRCULATIONAHA.108.827618","article-title":"Interleukin-17 and Interferon-\u03b3 Are Produced Concomitantly by Human Coronary Artery\u2013Infiltrating T Cells and Act Synergistically on Vascular Smooth Muscle Cells","volume":"119","author":"Eid","year":"2009","journal-title":"Circ."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1746","DOI":"10.1161\/CIRCULATIONAHA.109.924886","article-title":"Blockade of Interleukin-17A Results in Reduced Atherosclerosis in Apolipoprotein E\u2013Deficient Mice","volume":"121","author":"Smith","year":"2010","journal-title":"Circ."},{"key":"ref_34","first-page":"196ra100","article-title":"Transforming Growth Factor\u2013\u03b2 Signaling in T Cells Promotes Stabilization of Atherosclerotic Plaques Through an Interleukin-17\u2013Dependent Pathway","volume":"5","author":"Robertson","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/s41423-018-0004-4","article-title":"When worlds collide: Th17 and Treg cells in cancer and autoimmunity","volume":"15","author":"Knochelmann","year":"2018","journal-title":"Cell. Mol. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1126\/science.aaa8172","article-title":"The future of immune checkpoint therapy","volume":"348","author":"Sharma","year":"2015","journal-title":"Science"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/nri3405","article-title":"Molecular mechanisms of T cell co-stimulation and co-inhibition","volume":"13","author":"Chen","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1186\/s13045-016-0343-5","article-title":"Targeting of PI3K\/AKT\/mTOR pathway to inhibit T cell activation and prevent graft-versus-host disease development","volume":"9","author":"Almeida","year":"2016","journal-title":"J. Hematol. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"989431","DOI":"10.3389\/fphar.2022.989431","article-title":"The role of immune checkpoints in cardiovascular disease","volume":"13","author":"Yousif","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1093\/intimm\/dxq049","article-title":"PD-L1 and PD-L2 differ in their molecular mechanisms of interaction with PD-1","volume":"22","author":"Ghiotto","year":"2010","journal-title":"Int. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"9543","DOI":"10.1128\/MCB.25.21.9543-9553.2005","article-title":"CTLA-4 and PD-1 Receptors Inhibit T-Cell Activation by Distinct Mechanisms","volume":"25","author":"Parry","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1818","DOI":"10.1016\/j.celrep.2017.07.075","article-title":"PDL1 Signals through Conserved Sequence Motifs to Overcome Interferon-Mediated Cytotoxicity","volume":"20","author":"Zuazo","year":"2017","journal-title":"Cell Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1097\/COC.0000000000000239","article-title":"CTLA-4 and PD-1 Pathways: Similarities, Differences, and Implications of Their Inhibition","volume":"39","author":"Buchbinder","year":"2016","journal-title":"Am. J. Clin. Oncol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Ronen, D., Bsoul, A., Lotem, M., Abedat, S., Yarkoni, M., Amir, O., and Asleh, R. (2022). Exploring the Mechanisms Underlying the Cardiotoxic Effects of Immune Checkpoint Inhibitor Therapies. Vaccines, 10.","DOI":"10.3390\/vaccines10040540"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1002\/eji.202048747","article-title":"Combined anti-PD-1 and anti-CTLA-4 checkpoint blockade: Treatment of melanoma and immune mechanisms of action","volume":"51","author":"Willsmore","year":"2021","journal-title":"Eur. J. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Zhang, Q., Chikina, M., Szymczak-Workman, A.L., Horne, W., Kolls, J.K., Vignali, K.M., Normolle, D., Bettini, M., Workman, C.J., and Vignali, D.A.A. (2017). LAG3 limits regulatory T cell proliferation and function in autoimmune diabetes. Sci. Immunol., 2.","DOI":"10.1126\/sciimmunol.aah4569"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3418","DOI":"10.1158\/0008-5472.CAN-13-2690","article-title":"LSECtin Expressed on Melanoma Cells Promotes Tumor Progression by Inhibiting Antitumor T-cell Responses","volume":"74","author":"Xu","year":"2014","journal-title":"Cancer Res"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/j.immuni.2016.05.001","article-title":"Lag-3, Tim-3, and TIGIT: Co-inhibitory Receptors with Specialized Functions in Immune Regulation","volume":"44","author":"Anderson","year":"2016","journal-title":"Immunity"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1714","DOI":"10.1016\/j.jacc.2019.07.079","article-title":"Cardiovascular Toxicities of Immune Checkpoint Inhibitors","volume":"74","author":"Ball","year":"2019","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"H1052","DOI":"10.1152\/ajpheart.00024.2017","article-title":"Immune checkpoint dysfunction in large and medium vessel vasculitis","volume":"312","author":"Watanabe","year":"2017","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1016\/j.jaccao.2022.11.011","article-title":"Atherosclerosis With Immune Checkpoint Inhibitor Therapy","volume":"4","author":"Zanni","year":"2022","journal-title":"JACC CardioOncology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2974","DOI":"10.1172\/JCI31344","article-title":"Proatherogenic immune responses are regulated by the PD-1\/PD-L pathway in mice","volume":"117","author":"Gotsman","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1161\/ATVBAHA.111.224709","article-title":"Impairment of the Programmed Cell Death-1 Pathway Increases Atherosclerotic Lesion Development and Inflammation","volume":"31","author":"Bu","year":"2011","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.yjmcc.2008.10.028","article-title":"Contributions of PD-1\/PD-L1 pathway to interactions of myeloid DCs with T cells in atherosclerosis","volume":"46","author":"Lee","year":"2009","journal-title":"J. Mol. Cell Cardiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1093\/eurheartj\/ehab430","article-title":"Targeting early stages of cardiotoxicity from anti-PD1 immune checkpoint inhibitor therapy","volume":"43","author":"Michel","year":"2021","journal-title":"Eur. Hear. J."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Michel, L., Korste, S., Spomer, A., Hendgen-Cotta, U.B., Rassaf, T., and Totzeck, M. (2022). PD1 Deficiency Modifies Cardiac Immunity during Baseline Conditions and in Reperfused Acute Myocardial Infarction. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23147533"},{"key":"ref_57","first-page":"001779","article-title":"Relationship Between Cancer and Cardiovascular Outcomes Following Percutaneous Coronary Intervention","volume":"4","author":"Hess","year":"2015","journal-title":"J. Am. Hear. Assoc."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1161\/ATVBAHA.115.306848","article-title":"Overexpression of Cytotoxic T-Lymphocyte\u2013Associated Antigen-4 Prevents Atherosclerosis in Mice","volume":"36","author":"Matsumoto","year":"2016","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Poels, K., van Leent, M.M.T., Reiche, M.E., Kusters, P.J.H., Huveneers, S., de Winther, M.P.J., Mulder, W.J.M., Lutgens, E., and Seijkens, T.T.P. (2020). Antibody-Mediated Inhibition of CTLA4 Aggravates Atherosclerotic Plaque Inflammation and Progression in Hyperlipidemic Mice. Cells, 9.","DOI":"10.3390\/cells9091987"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1016\/j.ijcard.2012.12.085","article-title":"T-cell co-stimulation by CD28\u2013CD80\/86 and its negative regulator CTLA-4 strongly influence accelerated atherosclerosis development","volume":"168","author":"Ewing","year":"2013","journal-title":"Int. J. Cardiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1093\/cvr\/cvs330","article-title":"CTLA4-IgG ameliorates homocysteine-accelerated atherosclerosis by inhibiting T-cell overactivation in apoE\u2212\/\u2212 mice","volume":"97","author":"Ma","year":"2012","journal-title":"Cardiovasc. Res."},{"key":"ref_62","first-page":"e88628","article-title":"Lymphocyte activation gene 3 and coronary artery disease","volume":"1","author":"Golden","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"176","DOI":"10.18632\/genesandcancer.180","article-title":"The promising immune checkpoint LAG-3: From tumor microenvironment to cancer immunotherapy","volume":"9","author":"Long","year":"2018","journal-title":"Genes Cancer"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1172\/JCI1112","article-title":"Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine\/paracrine mechanisms involving TGF-beta, PGE2, and PAF","volume":"101","author":"Bratton","year":"1998","journal-title":"J. Clin. Investig."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e75","DOI":"10.1161\/ATVBAHA.117.309229","article-title":"Cell Death in the Vessel Wall","volume":"37","author":"Rayner","year":"2017","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1056\/NEJMc2029834","article-title":"Effect of CD47 Blockade on Vascular Inflammation","volume":"384","author":"Jarr","year":"2021","journal-title":"New Engl. J. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1038\/s41565-019-0619-3","article-title":"Pro-efferocytic nanoparticles are specifically taken up by lesional macrophages and prevent atherosclerosis","volume":"15","author":"Flores","year":"2020","journal-title":"Nat. Nanotechnol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1056\/NEJMoa1807315","article-title":"CD47 Blockade by Hu5F9-G4 and Rituximab in Non-Hodgkin\u2019s Lymphoma","volume":"379","author":"Advani","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1016\/j.immuni.2018.07.015","article-title":"Cells Promote Macrophage Efferocytosis during Inflammation Resolution","volume":"49","author":"Proto","year":"2018","journal-title":"Immunity"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1093\/carcin\/bgy088","article-title":"Metabolic influence on the differentiation of suppressive myeloid cells in cancer","volume":"39","author":"Porta","year":"2018","journal-title":"Carcinog."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.cmet.2019.04.002","article-title":"Cholesterol Induces CD8+ T Cell Exhaustion in the Tumor Microenvironment","volume":"30","author":"Ma","year":"2019","journal-title":"Cell Metab."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1097\/CJI.0000000000000321","article-title":"The Prognostic Role of High Blood Cholesterol in Advanced Cancer Patients Treated With Immune Checkpoint Inhibitors","volume":"43","author":"Perrone","year":"2020","journal-title":"J. Immunother."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e000821","DOI":"10.1136\/jitc-2020-000821","article-title":"Impact of body composition on outcomes from anti-PD1 +\/\u2212 anti-CTLA-4 treatment in melanoma","volume":"8","author":"Young","year":"2020","journal-title":"J. Immunother. Cancer"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.1161\/CIRCULATIONAHA.120.049981","article-title":"Association Between Immune Checkpoint Inhibitors With Cardiovascular Events and Atherosclerotic Plaque","volume":"142","author":"Drobni","year":"2020","journal-title":"Circ."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.ejca.2019.06.021","article-title":"Acute vascular events as a possibly related adverse event of immunotherapy: A single-institute retrospective study","volume":"120","author":"Bar","year":"2019","journal-title":"Eur. J. Cancer"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1001\/jamaoncol.2019.0393","article-title":"Treatment-Related Adverse Events of PD-1 and PD-L1 Inhibitors in Clinical Trials: A Systematic Review and Meta-analysis","volume":"5","author":"Wang","year":"2019","journal-title":"JAMA Oncol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1920","DOI":"10.1016\/j.amjcard.2020.02.016","article-title":"Cardiovascular Health and Outcomes in Cancer Patients Receiving Immune Checkpoint Inhibitors","volume":"125","author":"Oren","year":"2020","journal-title":"Am. J. Cardiol."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Nichetti, F., Ligorio, F., Zattarin, E., Signorelli, D., Prelaj, A., Proto, C., Galli, G., Marra, A., Apollonio, G., and Porcu, L. (2019). Is There an Interplay between Immune Checkpoint Inhibitors, Thromboprophylactic Treatments and Thromboembolic Events? Mechanisms and Impact in Non-Small Cell Lung Cancer Patients. Cancers, 12.","DOI":"10.3390\/cancers12010067"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2396","DOI":"10.1161\/CIRCULATIONAHA.120.048708","article-title":"Immune Checkpoint Inhibitor Therapy Induces Inflammatory Activity in Large Arteries","volume":"142","author":"Calabretta","year":"2020","journal-title":"Circ."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e007307","DOI":"10.1136\/jitc-2023-007307","article-title":"Impact of immune checkpoint inhibitors on atherosclerosis progression in patients with lung cancer","volume":"11","author":"Drobni","year":"2023","journal-title":"J. Immunother. Cancer"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"18531","DOI":"10.1002\/cam4.6455","article-title":"Association of immune checkpoint inhibitors therapy with arterial thromboembolic events in cancer patients: A retrospective cohort study","volume":"12","author":"Zhu","year":"2023","journal-title":"Cancer Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2315","DOI":"10.1093\/eurheartj\/ehw106","article-title":"2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts). Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR)","volume":"37","author":"Piepoli","year":"2016","journal-title":"Eur. Heart J."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Inno, A., Chiampan, A., Lanzoni, L., Verz\u00e8, M., Molon, G., and Gori, S. (2021). Immune Checkpoint Inhibitors and Atherosclerotic Vascular Events in Cancer Patients. Front. Cardiovasc. Med., 8.","DOI":"10.3389\/fcvm.2021.652186"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.1056\/NEJMoa1801174","article-title":"Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome","volume":"379","author":"Schwartz","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1056\/NEJMoa1615664","article-title":"Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease","volume":"376","author":"Sabatine","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1038\/s41586-020-2911-7","article-title":"Inhibition of PCSK9 potentiates immune checkpoint therapy for cancer","volume":"588","author":"Liu","year":"2020","journal-title":"Nature"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Quagliariello, V., Bisceglia, I., Berretta, M., Iovine, M., Canale, M.L., Maurea, C., Giordano, V., Paccone, A., Inno, A., and Maurea, N. (2023). PCSK9 Inhibitors in Cancer Patients Treated with Immune-Checkpoint Inhibitors to Reduce Cardiovascular Events: New Frontiers in Cardioncology. Cancers, 15.","DOI":"10.3390\/cancers15051397"},{"key":"ref_88","first-page":"883","article-title":"APP, APLP2 and LRP1 interact with PCSK9 but are not required for PCSK9-mediated degradation of the LDLR in vivo","volume":"1862","author":"Fu","year":"2017","journal-title":"Biochim. et Biophys. Acta (BBA) Mol. Cell Biol. Lipids"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"e2205105","DOI":"10.1002\/advs.202205105","article-title":"Biomaterial Strategies for Selective Immune Tolerance: Advances and Gaps","volume":"10","author":"Carey","year":"2023","journal-title":"Adv. Sci."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.atherosclerosis.2022.05.017","article-title":"Tim-1 mucin domain-mutant mice display exacerbated atherosclerosis","volume":"352","author":"Douna","year":"2022","journal-title":"Atherosclerosis"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.1021\/acsptsci.1c00145","article-title":"PCSK9 Axis-Targeting Pseurotin A as a Novel Prostate Cancer Recurrence Suppressor Lead","volume":"4","author":"Abdelwahed","year":"2021","journal-title":"ACS Pharmacol. Transl. Sci."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"24","DOI":"10.2174\/1389557521666211202115823","article-title":"A Comprehensive Review on PCSK9 as Mechanistic Target Approach in Cancer Therapy","volume":"23","author":"Saha","year":"2023","journal-title":"Mini-Reviews Med. Chem."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Xia, X.-D., Peng, Z.-S., Gu, H.-M., Wang, M., Wang, G.-Q., and Zhang, D.-W. (2021). Regulation of PCSK9 Expression and Function: Mechanisms and Therapeutic Implications. Front. Cardiovasc. Med., 8.","DOI":"10.3389\/fcvm.2021.764038"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1007\/s00262-019-02367-z","article-title":"Serum PCSK9 levels at the second nivolumab cycle predict overall survival in elderly patients with NSCLC: A pilot study","volume":"68","author":"Bonaventura","year":"2019","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2541","DOI":"10.1016\/j.nano.2018.08.008","article-title":"Enhanced chemo-immunotherapy against melanoma by inhibition of cholesterol esterification in CD8+ T cells","volume":"14","author":"Li","year":"2018","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Charbe, N.B., Lagos, C.F., Ortiz, C.A.V., Tambuwala, M., Palakurthi, S.S., and Zacconi, F.C. (2022). PCSK9 conjugated liposomes for targeted delivery of paclitaxel to the cancer cell: A proof-of-concept study. Biomed. Pharmacother., 153.","DOI":"10.1016\/j.biopha.2022.113428"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1993","DOI":"10.3892\/etm.2017.4218","article-title":"PCSK9 regulates apoptosis in human lung adenocarcinoma A549 cells via endoplasmic reticulum stress and mitochondrial signaling pathways","volume":"13","author":"Xu","year":"2017","journal-title":"Exp. Ther. Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13046-022-02477-0","article-title":"PCSK9 promotes the progression and metastasis of colon cancer cells through regulation of EMT and PI3K\/AKT signaling in tumor cells and phenotypic polarization of macrophages","volume":"41","author":"Wang","year":"2022","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-017-02358-7","article-title":"TNF\u03b1 blockade overcomes resistance to anti-PD-1 in experimental melanoma","volume":"8","author":"Bertrand","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1056\/NEJMoa1302369","article-title":"Nivolumab plus Ipilimumab in Advanced Melanoma","volume":"369","author":"Wolchok","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1084\/jem.20130579","article-title":"Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti\u2013CTLA-4 therapy against melanoma","volume":"210","author":"Simpson","year":"2013","journal-title":"J. Exp. Med."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.cell.2017.01.017","article-title":"Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy","volume":"168","author":"Sharma","year":"2017","journal-title":"Cell"},{"key":"ref_103","first-page":"635","article-title":"Cardiac Computed Tomography in Cardio-Oncology","volume":"3","author":"Yang","year":"2021","journal-title":"JACC: CardioOncology"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1007\/s10554-014-0370-7","article-title":"Predictors of change in carotid atherosclerotic plaque inflammation and burden as measured by 18-FDG-PET and MRI, respectively, in the dal-PLAQUE study","volume":"30","author":"Mani","year":"2014","journal-title":"Int. J. Cardiovasc. Imaging"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1161\/ATVBAHA.119.313455","article-title":"Atherosclerosis Immunoimaging by Positron Emission Tomography","volume":"40","author":"Fayad","year":"2020","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1093\/cvr\/cvx248","article-title":"Exploring immune checkpoints as potential therapeutic targets in atherosclerosis","volume":"114","author":"Kusters","year":"2018","journal-title":"Cardiovasc. Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13550-015-0157-4","article-title":"Preclinical imaging of the co-stimulatory molecules CD80 and CD86 with indium-111-labeled belatacept in atherosclerosis","volume":"6","author":"Meletta","year":"2016","journal-title":"EJNMMI Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1038\/28204","article-title":"Reduction of atherosclerosis in mice by inhibition of CD40 signalling","volume":"394","author":"Mach","year":"1998","journal-title":"Nature"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1210\/clinem\/dgz013","article-title":"A Novel Anti-CD40 Monoclonal Antibody, Iscalimab, for Control of Graves Hyperthyroidism\u2014A Proof-of-Concept Trial","volume":"105","author":"Kahaly","year":"2019","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1007\/s11307-016-0987-0","article-title":"CD80 Is Upregulated in a Mouse Model with Shear Stress-Induced Atherosclerosis and Allows for Evaluating CD80-Targeting PET Tracers","volume":"19","author":"Meletta","year":"2016","journal-title":"Mol. Imaging Biol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13045-021-01197-w","article-title":"Targeting CD47 for cancer immunotherapy","volume":"14","author":"Jiang","year":"2021","journal-title":"J. Hematol. Oncol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/5\/2502\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:02:08Z","timestamp":1760104928000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/5\/2502"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,21]]},"references-count":111,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["ijms25052502"],"URL":"https:\/\/doi.org\/10.3390\/ijms25052502","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,21]]}}}