Immune determinants of leuprolide-associated cardiovascular risk in prostate cancer

Abstract

Leuprolide, a widely used androgen-deprivation therapy (ADT) for prostate cancer (PC), has been associated with increased cardiovascular events (CVE), although the underlying mechanisms remain unclear. Through integrated spatial transcriptomic analyses of murine heart and immune-stromal profiling in patient blood, we identified immune programs linked to leuprolide-associated CVE risk. Spatial analyses revealed the distinct organization of lymphoid (T+B cells) aggregates and inflammatory macrophages in the plaque following leuprolide exposure that accompanied by ventricular hypertrophy, relative to normal vasculature. Parallel profiling of circulatory soluble and cellular components in patients demonstrated CD8+T cell enriched pattern in ~44% of patients, including memory and type 1 cytotoxic subsets that linked to treatment-induced CVE, such as ventricular dysfunctions, but no contribution of adipocytokines. These translational findings highlight the stratification of leuprolide-associated CVE risk in PC patients based on circulating T cell profiling and could guide the risk mitigation with alternative ADT agents.

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BibTeX RIS

BibTeX

@misc{gupta2026immune,
  title = {{Immune determinants of leuprolide-associated cardiovascular risk in prostate cancer}},
  author = {T. Gupta and F. Zeng and M. Li and I. Moore and V. C. Parihar and A. K. Yadalam and A. Ahluwalia and R. J. C. Reyes and Y. Chen and J. Hammons and E. Chung and H. Xu and S. Mecorapaj and M. Lu and R. Han and A. A. Quyyumi and G. B. Lesinski and E. K. Waller and B. Olsen and S. A. Patel and A. Mandawat and K. Chaudagar},
  howpublished = {bioRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.01.756122},
  url = {https://www.biorxiv.org/content/10.64898/2026.10.01.756122v1},
  note = {CC BY},
}

RIS

TY  - UNPB
TI  - Immune determinants of leuprolide-associated cardiovascular risk in prostate cancer
AU  - T. Gupta
AU  - F. Zeng
AU  - M. Li
AU  - I. Moore
AU  - V. C. Parihar
AU  - A. K. Yadalam
AU  - A. Ahluwalia
AU  - R. J. C. Reyes
AU  - Y. Chen
AU  - J. Hammons
AU  - E. Chung
AU  - H. Xu
AU  - S. Mecorapaj
AU  - M. Lu
AU  - R. Han
AU  - A. A. Quyyumi
AU  - G. B. Lesinski
AU  - E. K. Waller
AU  - B. Olsen
AU  - S. A. Patel
AU  - A. Mandawat
AU  - K. Chaudagar
PY  - 2026
DA  - 2026/10/01
PB  - bioRxiv
DO  - 10.64898/2026.10.01.756122
UR  - https://www.biorxiv.org/content/10.64898/2026.10.01.756122v1
AB  - Leuprolide, a widely used androgen-deprivation therapy (ADT) for prostate cancer (PC), has been associated with increased cardiovascular events (CVE), although the underlying mechanisms remain unclear. Through integrated spatial transcriptomic analyses of murine heart and immune-stromal profiling in patient blood, we identified immune programs linked to leuprolide-associated CVE risk. Spatial analyses revealed the distinct organization of lymphoid (T+B cells) aggregates and inflammatory macrophages in the plaque following leuprolide exposure that accompanied by ventricular hypertrophy, relative to normal vasculature. Parallel profiling of circulatory soluble and cellular components in patients demonstrated CD8+T cell enriched pattern in ~44% of patients, including memory and type 1 cytotoxic subsets that linked to treatment-induced CVE, such as ventricular dysfunctions, but no contribution of adipocytokines. These translational findings highlight the stratification of leuprolide-associated CVE risk in PC patients based on circulating T cell profiling and could guide the risk mitigation with alternative ADT agents.
ER  -

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