Immune Checkpoint Inhibitor-associated Myocarditis and Respiratory Failure in Pregnancy: A Translational Review of Cardio-oncology and Maternal–fetal Immunology

Immune checkpoint inhibitors were once considered incompatible with pregnancy, yet contemporary oncology practice increasingly encounters situations in which treatment and gestation intersect. As survival improves and therapeutic indications expand, clinicians are occasionally faced with the difficult task of balancing maternal cancer control against uncertain immunologic consequences during pregnancy. Myocarditis and immune-mediated pneumonitis, although uncommon, represent among the most serious immune-related toxicities of checkpoint blockade. The interaction between these toxicities and the distinctive immune environment of pregnancy remains poorly characterized and scattered across disparate clinical and mechanistic reports. This review synthesizes available literature describing immune checkpoint inhibitor exposure in pregnancy together with broader cardio-oncology and immunology studies that illuminate mechanisms of immune-related cardiopulmonary injury. Structured searches of biomedical databases and clinical registries identified 686 records; after duplicate removal and relevance screening, 36 studies were considered informative for narrative synthesis. These studies included pregnancy case reports and cohorts, mechanistic investigations, and clinical analyses of immune checkpoint inhibitor–associated myocarditis and pneumonitis. Although pregnancy-specific clinical evidence remains limited, convergent observations across the literature suggest biologically plausible links between checkpoint inhibition, disruption of programmed cell death protein 1/programmed death-ligand 1-mediated immune tolerance, and immune activation affecting cardiac and pulmonary tissues. Early biomarker abnormalities, particularly cardiac troponin elevation or subtle respiratory symptoms, may precede overt clinical deterioration. Recognition of these signals during pregnancy can be challenging because physiologic cardiopulmonary changes may obscure early manifestations of immune-mediated injury. Taken together, the available evidence indicates that pregnancy should be viewed not simply as a coincidental exposure context but as a distinct immunologic state in which checkpoint blockade may interact with maternal–fetal tolerance pathways. Careful surveillance, pregnancy-adapted diagnostic strategies, and multidisciplinary collaboration are therefore essential when immune checkpoint inhibitors are administered during gestation.