Checkpoint Inhibitors Not Linked to Increased Arterial Inflammation

Immune checkpoint inhibitors (ICIs), vascular endothelial growth factor inhibitors (VEGFIs), and their combination were not associated with increased arterial inflammation detectable by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) over 24 weeks in a prospective cohort study published in JAMA Cardiology.

The study included adults with cancer who were scheduled to receive ICI monotherapy, VEGFI monotherapy, or both within the West of Scotland regional cancer hospital network. Imaging and venous blood sampling were performed before treatment and at 24 weeks. The primary outcome was the between-group difference in change in maximal tissue-to-background ratio (TBRmax), adjusted for baseline. Researchers also evaluated systemic inflammatory biomarkers, plasma proteomics, and circulating immune-cell phenotypes.

Among 55 evaluable patients, the mean age was 66 years (SD, 10); 39 (71%) were male and 16 (29%) were female. Twenty received ICI therapy, 15 received VEGFI therapy, and 20 received combination therapy. TBRmax did not rise above baseline in any group at 24 weeks (among-group P=.13). Results were consistent across artery type, calcification status, prior atherosclerotic disease, and steroid exposure.

ICI therapy was associated with selective changes in T-cell subsets, which were attenuated with concurrent VEGFI therapy. VEGFI monotherapy was not significantly associated with changes in circulating immune cells, and systemic inflammatory biomarkers changed only modestly across all 3 regimens. Intracellular adhesion molecule-1 and vascular cell adhesion molecule-1 increased among patients exposed to ICIs.

Investigators concluded that the findings do not support macrophage-driven plaque activation as the primary mechanism of ICI-associated atherothrombosis. They said the results instead support prioritizing endothelial and thrombotic pathways in future mechanistic and preventive studies.

Source: Rankin S, MacRitchie N, Morsy MI, et al. PET, proteomics, and immunophenotyping of arterial inflammation and checkpoint inhibition. JAMA Cardiol. Published online September 9, 2026. doi:10.1001/jamacardio.2026.3443