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Adv."],"published-print":{"date-parts":[[2026,8,28]]},"abstract":"<jats:p>\n                    Immune checkpoint inhibitor (ICI) myocarditis is a rare but frequently fatal immune-related adverse event of cancer immunotherapy. Understanding the mechanisms of this toxicity is critical to balancing treatment with maintenance of antitumor immunity. Using integrated spatial and single-cell analyses in a pharmacological murine model, we identified regional infiltration of Ly6C\n                    <jats:sup>+<\/jats:sup>\n                    monocytes and PD-1\n                    <jats:sup>+<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells in the heart that organize into fibroblast-rich immune structures, which we term tertiary T cell niches (TTCNs). TTCNs serve as hubs for T cell activation, sharing features of tertiary lymphoid structures. A TTCN gene signature was strongly enriched in cardiac tissue from patients with ICI myocarditis. Complementary T cell receptor analyses revealed clonal expansion of cardiac T cells following ICI treatment. We further identified TTCN-associated cytokines and structural proteins as candidate therapeutic targets to reduce myocardial inflammation while considering tumor control. Together, these findings suggest that cardiac tertiary immune structures play a central role in ICI myocarditis and highlight pathways that could mitigate ICI cardiotoxicity.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aed8359","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T17:59:39Z","timestamp":1787767179000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Cardiac tertiary immune niches drive immune activation in immune checkpoint inhibitor myocarditis"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2682-4051","authenticated-orcid":true,"given":"Carly C.","family":"Tymm","sequence":"first","affiliation":[{"name":"Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA."},{"name":"Division of Rheumatology, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3536-861X","authenticated-orcid":true,"given":"Matthieu","family":"Paiola","sequence":"additional","affiliation":[{"name":"Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoiab","family":"Bukhari","sequence":"additional","affiliation":[{"name":"Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2192-6185","authenticated-orcid":true,"given":"Xizi","family":"Hu","sequence":"additional","affiliation":[{"name":"Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7543-8037","authenticated-orcid":true,"given":"Robert","family":"Winchester","sequence":"additional","affiliation":[{"name":"Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA."},{"name":"Division of Rheumatology, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2854-2405","authenticated-orcid":true,"given":"Adam","family":"Mor","sequence":"additional","affiliation":[{"name":"Columbia Center for Translational Immunology, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA."},{"name":"Division of Rheumatology, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA."},{"name":"Herbert Irvine Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/1759-7714.13541"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-024-00715-5"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1609214"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1455347"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaccao.2024.07.002"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardfail.2019.07.357"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-22-3181"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2023-008482"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.122.062551"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-08105-5"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.121.056730"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-24-0011"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111611"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05432-3"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/cas.14591"},{"key":"e_1_3_2_17_2","doi-asserted-by":"crossref","unstructured":"M. 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