Metabolic pathways regulate cardiovascular toxicity in cancer immunotherapy

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, yet their clinical application is constrained by a critical trade-off between potent antitumor efficacy and off-target cardiovascular toxicity. This adverse effect underscores a fundamental biological dilemma: how tumor immunotherapy disrupts cardiovascular homeostasis. Immune cells within the cardiovascular system undergo metabolic adaptations after immune therapy. This intricate crosstalk has brought metabolic checkpoints to the forefront of research. In this review, we systematically outline the features of tumor-associated metabolic remodeling and shared roles in cardiac metabolism and immunometabolism. We elucidate ICIs initiate a cascade of events leading to cardic dysfunction through metabolic signal pathways. Furthermore, we propose that the strategic integration of cutting-edge technologies including spatial metabolomics to enable precise reprogramming of metabolic networks will ultimately decouple the efficacy of cancer immunotherapy from its associated toxicities.