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

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  Figure 1. Classification and clinical impact of cardiac tumors and cardiac metastases. Cardiac tumors can be broadly divided into primary cardiac tumors and cardiac metastases. Primary cardiac tumors include benign lesions, such as cardiac myxoma, and malignant tumors, most commonly cardiac sarcomas, with major subtypes including angiosarcoma, undifferentiated sarcoma, intimal sarcoma, and leiomyosarcoma. Cardiac metastases arise from extracardiac malignancies, including lung cancer, breast cancer, melanoma, lymphoma, renal cell carcinoma, Merkel cell carcinoma, and nasopharyngeal carcinoma. Although primary cardiac tumors are rare, cardiac metastases are more common; both may cause clinically significant cardiovascular complications, including intracardiac obstruction, embolism, arrhythmias, pericardial effusion or tamponade, myocardial infiltration, heart failure-like symptoms, and diagnostic overlap with therapy-related cardiotoxicity.

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  Figure 2. Cardio-immuno-oncology framework in cardiac tumors and cardiac metastases. The cardiac tumor immune ecosystem is shaped by interactions among tumor cells, immune cells, cytokine gradients, hypoxic regions, metabolic stress, and the vascular microenvironment. Immunosuppressive mechanisms, including M2 macrophages, regulatory T cells, exhausted PD-1+ CD8+ T cells, PD-L1-mediated immune inhibition, CD47–SIRPα signaling, hypoxia, lactate accumulation, and IL-10/TGF-β suppressive signaling, may promote immune escape and tumor progression. Therapeutic interventions, including PD-1/PD-L1 blockade, CTLA-4 inhibition, anti-VEGF therapy, radiotherapy, tyrosine kinase inhibitors (TKIs), and combination immunotherapy, may restore antitumor immune activity, enhance CD8+ T-cell function, normalize tumor vasculature, and promote tumor suppression. However, therapeutic immune activation must be balanced against cardiovascular risk, including myocarditis, arrhythmias, and heart failure, highlighting the need for cardiovascular surveillance with ECG, cardiac troponin assessment, and echocardiography. Several mechanisms depicted in this conceptual framework are supported primarily by evidence from…

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  Figure 3. Multi-omics decoding of tumor immunity in cardiac tumors and cardiac metastases. Multi-omics approaches, including single-cell RNA sequencing, spatial transcriptomics, proteomics, metabolomics, and integrative multi-omics analysis, provide complementary insights into the cardiac tumor microenvironment. These technologies help reveal cellular heterogeneity, spatial immune organization, tumor–stromal interactions, immune-evasion pathways, cytokine signaling, metabolic reprogramming, and vascular abnormalities. Integration of these findings may facilitate immune biomarker discovery, patient stratification, therapeutic target identification, prediction of immunotherapy response, and cardiovascular risk-informed treatment, thereby supporting precision cardio-immuno-oncology strategies in cardiac tumors and cardiac metastases.

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  Figure 4. Future roadmap for precision cardio-immuno-oncology in cardiac tumors and cardiac metastases. This roadmap summarizes the major steps required to advance the field from current challenges toward precision cardio-immuno-oncology. Current barriers include the rarity of cardiac tumors, limited prospective evidence, heterogeneous tumor biology, unclear predictive biomarkers, and overlap between tumor-related cardiac involvement and treatment-related cardiotoxicity. Future progress will require collaborative evidence generation, standardized imaging response criteria, integrated cardiac safety endpoints, multi-omics-based biomarker discovery, rational therapeutic optimization, and cardiovascular risk-adapted management. Ultimately, precision cardio-immuno-oncology should integrate individualized treatment selection, biomarker-guided immunotherapy, and careful balancing of antitumor efficacy with cardiovascular safety.