
Yin Sun
Postdoctoral Scholar, Cardiovascular Institute
Honors & Awards
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AHA Postdoctoral Fellowship, American Heart Association (2025/01-2026/12)
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Excellent doctoral dissertations in Liaoning Province, Education Department of Liaoning Province (2024)
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Outstanding Doctoral Graduate in Liaoning Province, Educational Department of Liaoning Province (2023)
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National Fellowship for Doctoral Student, Ministry of Education, PRC (2022)
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Excellent Graduate Student in Shenyang, Shenyang Bureau Of Education (2022)
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"Xtalpi" Fellowship, XtalPi Inc. (2021)
Professional Education
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Ph.D., Shenyang Pharmaceutical University, Medicinal Chemistry (2023)
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Joint-training Master, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Medicinal Chemistry (2020)
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B.S., Shenyang Pharmaceutical University, Pharmacy (2018)
All Publications
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Novel Therapeutic Approach Targeting CXCR3 to Treat Immunotherapy Myocarditis.
Circulation research
2025
Abstract
Immune checkpoint inhibitors (ICIs) are successful in treating many cancers but may cause immune-related adverse events. ICI-mediated myocarditis has a high fatality rate with severe cardiovascular consequences. Targeted therapies for ICI myocarditis are currently limited.We used a genetic mouse model of PD1 deletion (MRL/Pdcd1-/-) along with a novel drug-treated ICI myocarditis mouse model to recapitulate the disease phenotype. We performed single-cell RNA-sequencing, single-cell T-cell receptor sequencing, and cellular indexing of transcriptomes and epitopes on immune cells isolated from MRL and MRL/Pdcd1-/- mice at serial time points. We assessed the impact of macrophage deletion in MRL/Pdcd1-/- mice, then inhibited CXCR3 (C-X-C motif chemokine receptor 3) in ICI-treated mice to assess the therapeutic effect on myocarditis phenotype. Furthermore, we delineated the functional and mechanistic effects of CXCR3 blockade on T-cell and macrophage interactions. We then correlated the results in human single-cell multiomics data from blood and heart biopsy data from patients with ICI myocarditis.Single-cell multiomics demonstrated expansion of CXCL (C-X-C motif chemokine ligand) 9/10+CCR2+ macrophages and CXCR3hi (C-X-C motif chemokine receptor 3 high-expressing) CD8+ (cluster of differentiation) effector T lymphocytes in the hearts of MRL/Pdcd1-/- mice correlating with onset of myocarditis development. Both depletion of CXCL9/10+CCR2+ (C-C motif chemokine receptor) macrophages and CXCR3 blockade, respectively, led to decreased CXCR3hi CD8+ T-cell infiltration into the heart and significantly improved survival. Transwell migration assays demonstrated that the selective blockade of CXCR3 and its ligand, CXCL10, reduced CXCR3+CD8+ T-cell migration toward macrophages, implicating this interaction in T-cell cardiotropism toward cardiac macrophages. Furthermore, cardiomyocyte apoptosis was induced by CXCR3hi CD8+ T cells. Cardiac biopsies from patients with confirmed ICI myocarditis demonstrated infiltrating CXCR3+ T cells and CXCL9+/CXCL10+ macrophages. Both mouse cardiac immune cells and patient peripheral blood immune cells revealed expanded TCR s (T-cell receptors) correlating with CXCR3hi CD8+ T cells in ICI myocarditis samples.These findings bring forth the CXCR3-CXCL9/10 axis as an attractive therapeutic target for ICI myocarditis treatment, and more broadly as a druggable pathway in cardiac inflammation.
View details for DOI 10.1161/CIRCRESAHA.124.325652
View details for PubMedID 39931812