{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T16:05:14Z","timestamp":1783353914437,"version":"3.54.6"},"reference-count":36,"publisher":"BMJ","issue":"5","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"unspecified","delay-in-days":27,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Fudan University Zhongshan Hospital Research and Development Fund","award":["2024ZSFZ64"],"award-info":[{"award-number":["2024ZSFZ64"]}]},{"name":"Fudan University Zhongshan Hospital Research and Development Fund","award":["2025ZSFZ34"],"award-info":[{"award-number":["2025ZSFZ34"]}]},{"name":"Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences","award":["2024-JKCS-28"],"award-info":[{"award-number":["2024-JKCS-28"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170359"],"award-info":[{"award-number":["82170359"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82470354"],"award-info":[{"award-number":["82470354"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Noncommunicable Chronic Diseases-National Science and Technology Major Project","award":["2023ZD0502800"],"award-info":[{"award-number":["2023ZD0502800"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2026,4,13]]},"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Immune checkpoint inhibitor-associated myocarditis (ICIAM) poses significant challenges for cancer immunotherapy, particularly regarding the safety and efficacy of immune checkpoint blockade (ICB) rechallenge.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The present study analyzed 23 cases of ICIAM by integrating longitudinal clinical data with single-cell RNA sequencing and T-cell receptor profiling of peripheral blood mononuclear cells (PBMCs) obtained from three representative patients before and after ICB rechallenge. The single-cell cohort comprised two patients who experienced recurrent irAEs upon rechallenge and one patient who did not develop recurrent irAEs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 12 patients (52%) who experienced recurrent irAEs upon rechallenge, myocarditis recurrence occurred in 8 cases, with most (88%) presenting as grade 1\u2014 significantly milder than initial episodes (p=0.046). Single-cell analysis revealed that the patient who did not develop recurrent irAEs exhibited a high proportion of effector CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells with high TRAV19 expression (CD8 Teff TRAV19), a TCR V\u03b1 family associated with SARS-CoV-2 reactivity. In contrast, patients who experienced recurrent irAEs lacked this expanded population. Rechallenge during myocarditis course was associated with higher recurrent irAEs risk (OR=14.0, 95%CI:1.3-147.4, p=0.027). Despite recurrence, tumor response was preserved, with a median progression-free survival (mPFS) of 8.5 months and no significant outcome difference between patients with and without post-rechallenge irAEs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>ICB rechallenge is feasible in selected ICIAM patients, with most recurrent myocarditis cases being milder. Our exploratory single-cell analysis reveals that a high proportion of CD8 Teff TRAV19 was present in the patient protected from recurrence but absent in those who relapsed, suggesting that pre-existing virus specific memory T cells may modulate recurrent irAEs risk via antigen-specific niche occupation. While limited by sample size, these findings generate the hypothesis that T-cell repertoire composition could inform patient selection for ICB rechallenge, a concept warranting validation in larger cohorts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2025-014290","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T15:20:16Z","timestamp":1779981616000},"page":"e014290","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Clonal reshaping and clinical outcomes after rechallenge in ICI-associated myocarditis: integrated single-cell and TCR repertoire analysis"],"prefix":"10.1136","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7448-0856","authenticated-orcid":false,"given":"Jian","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China"},{"name":"State Key Laboratory of 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