Immune Pathways in Doxorubicin Cardiotoxicity: A Cardio-Immunology Perspective
- 1Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center “Guido Tarone”, University of Torino, Torino, Italy
- 2University of Texas Medical Branch, Galveston, Texas, USA
Abstract
Anthracyclines such as doxorubicin remain central to cancer therapy, but their clinical utility is constrained by dose-limiting cardiotoxicity and long-term cardiovascular sequelae. Although traditionally attributed to cardiomyocyte-intrinsic mechanisms, including mitochondrial dysfunction, oxidative stress, and DNA damage, emerging evidence demonstrates that these initial injuries rapidly activate the immune system, transforming doxorubicin-induced cardiotoxicity (DIC) into a multicellular inflammatory process. Release of mitochondrial and nuclear danger signals triggers innate immune pathways and recruitment of neutrophils, monocytes, and lymphocytes, whose sustained activation promotes maladaptive remodeling, fibrosis, and chronic dysfunction. Conversely, specific immune subsets exert context-dependent cardioprotective effects, underscoring the dual role of immune responses in disease progression. This review frames DIC within a cardioimmunology paradigm, highlighting the intersection of mitochondrial stress, sterile inflammation, and adaptive immunity across acute and chronic phases of injury. We discuss emerging therapeutic strategies that extend beyond cardiomyocyte protection, including immune recalibration rather than broad immunosuppression, immune-targeted interventions, and biomarker-guided monitoring, to enable mechanism-based, individualized cardioprotection without compromising anticancer efficacy.
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BibTeX
@article{guerra2026immune,
title = {{Immune Pathways in Doxorubicin Cardiotoxicity: A Cardio-Immunology Perspective}},
author = {Giulia Guerra and George Bianco and Alessandra Ghigo},
journal = {JACC: CardioOncology},
year = {2026},
month = aug,
doi = {10.1016/j.jaccao.2026.06.008},
url = {https://doi.org/10.1016/j.jaccao.2026.06.008},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Immune Pathways in Doxorubicin Cardiotoxicity: A Cardio-Immunology Perspective
AU - Giulia Guerra
AU - George Bianco
AU - Alessandra Ghigo
PY - 2026
DA - 2026/08/05
JO - JACC: CardioOncology
DO - 10.1016/j.jaccao.2026.06.008
UR - https://doi.org/10.1016/j.jaccao.2026.06.008
AB - Anthracyclines such as doxorubicin remain central to cancer therapy, but their clinical utility is constrained by dose-limiting cardiotoxicity and long-term cardiovascular sequelae. Although traditionally attributed to cardiomyocyte-intrinsic mechanisms, including mitochondrial dysfunction, oxidative stress, and DNA damage, emerging evidence demonstrates that these initial injuries rapidly activate the immune system, transforming doxorubicin-induced cardiotoxicity (DIC) into a multicellular inflammatory process. Release of mitochondrial and nuclear danger signals triggers innate immune pathways and recruitment of neutrophils, monocytes, and lymphocytes, whose sustained activation promotes maladaptive remodeling, fibrosis, and chronic dysfunction. Conversely, specific immune subsets exert context-dependent cardioprotective effects, underscoring the dual role of immune responses in disease progression. This review frames DIC within a cardioimmunology paradigm, highlighting the intersection of mitochondrial stress, sterile inflammation, and adaptive immunity across acute and chronic phases of injury. We discuss emerging therapeutic strategies that extend beyond cardiomyocyte protection, including immune recalibration rather than broad immunosuppression, immune-targeted interventions, and biomarker-guided monitoring, to enable mechanism-based, individualized cardioprotection without compromising anticancer efficacy.
SN - 2666-0873
ER -