Microbiota-indole-3-propionic acid-heart axis mediates the protection of leflunomide against αPD1-induced cardiotoxicity in mice.

ABSTRACT: Anti-programmed death 1 (αPD1) immune checkpoint blockade is used in combination for cancer treatment but associated with cardiovascular toxicity. Leflunomide (Lef) can suppress the growth of several tumor and mitigate cardiac remodeling in mice. However, the role of Lef in αPD1-induced cardiotoxicity remains unclear. Here, we report that Lef treatment inhibits αPD1-related cardiotoxicity without compromising the efficacy of αPD1-mediated immunotherapy. Lef changes community structure of gut microbiota in αPD1-treated melanoma-bearing mice. Moreover, mice receiving microbiota transplants from Lef+αPD1-treated melanoma-bearing mice have better cardiac function compared to mice receiving transplants from αPD1-treated mice. Mechanistically, we analyze metabolomics and identify indole-3-propio

SUBMITTER: Huang R 

PROVIDER: S-EPMC11923180 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature