Is the cardio-immune microenvironment a convergent hub of cardiovascular toxicity across novel anticancer therapies?
4 affiliations
- 1Department of Radiology, West China Hospital, Sichuan University
- 2Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
- 3Outpatient Department, West China Hospital, Sichuan University
- 4West China School of Medicine, Sichuan University
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.
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BibTeX
@article{quan2026cardioimmune,
title = {{Is the cardio-immune microenvironment a convergent hub of cardiovascular toxicity across novel anticancer therapies?}},
author = {Youzhuo Quan and Chunlan Lang and Peiliang Xie and Yun Zhang},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1980237},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1980237/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Is the cardio-immune microenvironment a convergent hub of cardiovascular toxicity across novel anticancer therapies?
AU - Youzhuo Quan
AU - Chunlan Lang
AU - Peiliang Xie
AU - Yun Zhang
PY - 2026
DA - 2026/10/29
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1980237
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1980237/full
AB - 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.
SN - 1663-9812
ER -