Cancer therapy may increase the risk of heart attacks and strokes by disrupting immune regulation in the arteries.

They investigated how diabetes mellitus and lipid-lowering therapy impact immune interactions in arterial plaques. By creating a map of immune checkpoint expression, the authors of the study aimed to understand the potential cardiovascular risks associated with the use of immune checkpoint inhibitors in the context of cancer treatment.

In this study, researchers analyzed the expression of immune checkpoints in human atherosclerotic plaques. They examined carotid plaques from 22 patients who underwent carotid endarterectomy.

Additionally, extensive ligand-receptor interaction mapping was conducted to explore cell communication mediated by immune checkpoints, focusing on molecules such as CTLA4, PD-1, LAG3, and others targeted by the immune checkpoint inhibitors studied, which have been approved by the Food and Drug Administration (FDA) for cancer treatment.

The study also evaluated the impact of cardiometabolic factors by assessing the expression of immune checkpoint genes in plaques from patients with diabetes and those without, as well as from individuals receiving lipid-lowering therapy.

Moreover, lipid-modifying interventions were performed on mice to understand the role of cholesterol in the dynamics of immune checkpoint function.

The research included data analysis, utilizing spatial mapping and multiplex immunofluorescence methods to confirm the findings. Immune interactions were examined through AI-based cell segmentation and digital pathology diagnostics. Pathway analysis was also conducted to identify immune regulatory networks and the influence of immune checkpoint expression on plaque inflammation.

Results

Overall, the study demonstrated the complex role of immune checkpoints in the progression of atherosclerosis, which is further shaped by cardiometabolic factors and immunomodulatory therapy.

The findings indicated that immune checkpoint inhibitors might exacerbate plaque inflammation.

The results provided insights on how to reduce cardiovascular risks in cancer patients undergoing treatment with immune checkpoint inhibitors and laid the groundwork for developing safer therapeutic strategies.