Additionally, the use of conventional CV drugs to counteract ICIs detrimental effects should be investigated. that this large immune cell infiltrates predominantly consisted of cytotoxic T cells and macrophages, suggesting that both lymphoid and myeloid immune cells drive inflammation in ICI-associated myocarditis.16 Although the majority of acute IRAEs can be overcome by corticosteroid treatment and temporary or permanent discontinuation of ICI therapy, these toxicities may severely compromise the clinical outcome and quality of life of patients with Deguelin cancer and long-term survivors.3 17 18 In addition to these acute IRAEs, ICI therapy may also affect the clinical course of pre-existing autoimmune diseases and other more gradually developing inflammatory conditions.19C21 For example, 27%C75% of the patients with cancer and a history of rheumatoid arthritis, systemic lupus erythematosus, or inflammatory bowel disease experienced a flare-up on ICI treatment.22C24 An important additional concern is the effect of ICIs on atherosclerosis, a chronic lipid-driven inflammatory disease of the larger arteries and a major underlying cause of cardiovascular disease (CVD), including myocardial infarction and ischemic stroke.21 25 Subclinical atherosclerosis is common and found in 45%C75% of the patients with cancer.26 27 As cancer and atherosclerosis share several risk factors, such as aging, a sedentary lifestyle, smoking and chronic low-grade inflammation, patients with cancer may be more susceptible to develop clinical complications of atherosclerosis, such as myocardial or cerebral infarction.27 Although preclinical studies identified a protective role for the immune checkpoint proteins CTLA4, PD1 and PDL1 in experimental atherosclerosis, clinical data on the effects of ICI-mediated inhibition of these proteins on atherosclerotic CVD were sparse. However, recently, several clinical studies have provided a new perspective on the effects of ICI therapy on atherosclerosis.27C31 Here we discuss the effects of ICI therapy on atherosclerosis in patients with cancer and explore the pathophysiology of ICI-related atherosclerotic CVD. Furthermore, we discuss potential strategies to reduce the impact of atherosclerotic CVD on ICI-treated patients with cancer. ICI therapy is usually associated with atherosclerotic CV events Until recently, clinical studies on the effect of ICIs on atherosclerosis were mainly limited to case reports and smaller cohort studies.27C29 32 In a larger study, Bar retrospectively analyzed the incidence of acute vascular complications among 1215 patients with cancer who received ICI therapy.30 Approximately 1% of the patients developed a myocardial infarction or ischemic stroke within 6 months after initiation of ICI treatment.30 Additionally, a recently published systematic review analyzed the incidence of arterial thrombotic events, in particular stroke and myocardial infarction, following ICI therapy.33 Among 17 studies, with a total of 10.106 subjects, the incidence rate of arterial thrombotic events in ICI-treated patients was 1.1%.33 The risk was independent of single or combination ICI treatment, but did seem associated with some cancer types with high thrombogenic properties, such as pancreatic and advanced genitourinary cancer.33 34 Despite the high level of evidence a systematic Deguelin review offers, determining the proportion of arterial thrombotic event attributable to ICIs alone remains complex thus far. The included retrospective studies might have suffered from selection bias, and prospective studies had a short follow-up and limited external validity due to their selection criteria. Information on concomitant or previous use of glucocorticoids, chemotherapy and radiotherapy is usually often not reported. These limitations hamper the translation of these retrospective data to everyday clinical practice. A recent publication of Drobni provides more detailed insights into the association between ICI therapy and atherosclerotic CVD in patients with cancer.31 This study investigated the incidence of atherosclerotic CV events, defined as a composite of Deguelin myocardial infarction, coronary revascularization, and ischemic stroke, in a cohort of 2842 patients with cancer, with a median age of 64 years who underwent ICI therapy and a control group of patients with cancer who did not undergo ICI treatment.31 Non-small cell lung cancer (NSCLC) and melanoma were the most common cancer types in the ICI-treated cohort and the majority of patients (75.3%) was treated with PD1 inhibitors, with a median treatment duration of five cycles. Although Mef2c the control group was matched for age, CV history, and cancer type, the presence of classical CV risk factors, including hypertension, hyperlipidemia and diabetes mellitus, was.