Immune determinants of leuprolide-associated cardiovascular risk in prostate cancer

Leuprolide, an androgen-deprivation therapy commonly used in prostate cancer treatment, has been linked to a heightened risk of cardiovascular events. However, the underlying reasons for this correlation have yet to be fully understood. In an effort to uncover these mechanisms, researchers employed spatial transcriptomic analyses of mouse heart tissue and immune-stromal profiling of patient blood samples.

This approach allowed them to identify distinct immune programs associated with the increased CVE risk associated with leuprolide exposure.

Through spatial analyses, the researchers observed unique patterns of lymphoid aggregates composed of T and B cells, as well as inflammatory macrophages, in plaque regions of the heart following leuprolide exposure. This was in contrast to the normal vasculature structure. Additionally, blood samples from patients treated with leuprolide revealed a significant CD8+T cell enrichment pattern in approximately 44% of cases.

This pattern included memory and type 1 cytotoxic subsets, which were linked to treatment-induced CVE, such as ventricular dysfunction. Importantly, the researchers found no contribution from adipocytokines in these outcomes.

These findings emphasize the importance of stratifying leuprolide-associated CVE risk in prostate cancer patients based on circulating T cell profiling. By doing so, doctors may be able to better predict which patients are at higher risk and potentially alter their treatment plans to mitigate this risk. This could be achieved through the use of alternative ADT agents, which might prove to be a more heart-healthy option for prostate cancer patients.