Work

Is the cardio-immune microenvironment a convergent hub of cardiovascular toxicity across novel anticancer therapies?

Year: 2026

Type: article

Abstract: Novel anticancer therapies have transformed oncology but have also expanded the spectrum of cancer therapy–related cardiovascular toxicity, including myocarditis, ventricular dysfunction, hypertension, vascular inflammation, thrombosis, arrhythmias, fibrosis, and heart failure. In cardio-oncology, the cardio-immune microenvironment provides a useful framework for integrating cardiovascular toxicity across immune checkpoint inhibitors, CAR-T cell therapy and other T-cell–redirecting therapies, HER2-directed therapies, VEGF/VEGFR inhibitors, antibody–drug conjugates, radiotherapy-containing regimens, and combination treatments. This Review discusses the cardio- immune microenvironment as a tissue-level network in which immune cells, cardiomyocytes, endothelial cells, vascular cells, fibroblasts, soluble mediators, and extracellular-matrix cues interact during injury and repair. Rather than proposing a universal immune origin for all cardiotoxic effects, we distinguish three routes by which novel anticancer treatments may enter this network: immune initiation, systemic inflammatory translation, and primary cardiomyocyte, endothelial, vascular, or payload-related injury followed by immune amplification and remodeling. We define mechanistically meaningful convergence as engagement of a shared downstream cellular–molecular response module by therapies with distinct proximal mechanisms, while distinguishing such convergence from nonspecific injury–repair responses. We organize the cardio-immune framework around five mechanistic domains: immune tolerance breakdown, cytokine-driven systemic inflammation, sterile danger sensing, myeloid and stromal reprogramming, and endothelial–immune coupling. We further discuss how these mechanisms may inform therapy-specific risk stratification, biomarker interpretation, imaging surveillance, mechanism-guided intervention, and multi-omics approaches in precision cardio-oncology. This context-dependent framework may help clarify why distinct anticancer therapies can produce overlapping cardiovascular phenotypes while preserving therapy-specific mechanisms and clinical management priorities.

Source: Frontiers in Pharmacology

DOI: 10.3389/fphar.2026.1980237

Authors: Youzhuo Quan, Chunlan Lang, Peiliang Xie, Yun Zhang

Institutions: Sichuan University, West China Hospital of Sichuan University, Huazhong University of Science and Technology

Language: English

Topic: Chemotherapy-induced cardiotoxicity and mitigation

Subfield: Cardiology and Cardiovascular Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801