Cardio-immuno-oncology in cardiac tumors and cardiac metastases: immune microenvironment, therapeutic opportunities, and cardiotoxicity.

Primary cardiac tumors are rare, whereas cardiac metastases are more common forms of cardiac involvement in patients with advanced malignancies; both are clinically important because of their potential cardiovascular consequences. This review summarizes current evidence on the immune microenvironment, immune-evasion mechanisms, immunotherapeutic opportunities, multi-omics-based immune decoding, and cardiovascular toxicity in cardiac tumors and cardiac metastases. Cardiac myxoma is discussed as a benign primary cardiac tumor with inflammatory, cytokine-mediated, metabolic, and candidate immune-regulatory features, whereas malignant primary cardiac tumors, particularly cardiac sarcomas such as cardiac angiosarcoma, are reviewed in relation to immunosuppressive niches, macrophage-rich microenvironments, T-cell dysfunction, and heterogeneous responses to immune checkpoint inhibitors. Cardiac metastases are considered as a clinically relevant setting in which immunotherapy may be feasible for selected patients with careful cardiovascular assessment. Key mechanisms discussed include immune checkpoint pathways, tumor-associated macrophages, metabolic reprogramming, cytokine signaling, vascular abnormalities, and spatial immune organization. The review also highlights the role of single-cell sequencing, spatial transcriptomics, proteomics, metabolomics, and integrative multi-omics approaches in defining tumor-specific immune landscapes and potential biomarkers. Finally, immune checkpoint inhibitor-associated cardiotoxicity, particularly myocarditis, is discussed with emphasis on baseline cardiovascular assessment, biomarker monitoring, multimodality imaging, and multidisciplinary cardio-oncology management.