Clonal reshaping and clinical outcomes after rechallenge in ICI-associated myocarditis: integrated single-cell and TCR repertoire analysis.
J, Z., X, H., Y, Z., X, Q., Y, S., S, Z., Z, L., Z, W., B, L., & Q, C. (2026). Clonal reshaping and clinical outcomes after rechallenge in ICI-associated myocarditis: integrated single-cell and TCR repertoire analysis.. Journal for immunotherapy of cancer. https://doi.org/10.1136/jitc-2025-014290
J Z, X H, Y Z, X Q, Y S, S Z, et al. Clonal reshaping and clinical outcomes after rechallenge in ICI-associated myocarditis: integrated single-cell and TCR repertoire analysis.. Journal for immunotherapy of cancer. 2026; doi: 10.1136/jitc-2025-014290
J Z, X H, Y Z, et al. Clonal reshaping and clinical outcomes after rechallenge in ICI-associated myocarditis: integrated single-cell and TCR repertoire analysis.[J]. Journal for immunotherapy of cancer. 2026. DOI: 10.1136/jitc-2025-014290.
@article{j2026,
author = {Zhang J and He X and Zhang Y and Qian X and Song Y and Zhang S and Li Z and Wang Z and Lu B and Cai Q},
title = {Clonal reshaping and clinical outcomes after rechallenge in ICI-associated myocarditis: integrated single-cell and TCR repertoire analysis.},
journal = {Journal for immunotherapy of cancer},
year = {2026},
doi = {10.1136/jitc-2025-014290},
note = {PMID: 42208979},
}
TY - JOUR AU - Zhang J AU - He X AU - Zhang Y AU - Qian X AU - Song Y AU - Zhang S AU - Li Z AU - Wang Z AU - Lu B AU - Cai Q TI - Clonal reshaping and clinical outcomes after rechallenge in ICI-associated myocarditis: integrated single-cell and TCR repertoire analysis. T2 - Journal for immunotherapy of cancer PY - 2026 DO - 10.1136/jitc-2025-014290 AN - PMID:42208979 ER -
BACKGROUND: Immune checkpoint inhibitor-associated myocarditis (ICIAM) poses significant challenges for cancer immunotherapy, particularly regarding the safety and efficacy of immune checkpoint blockade (ICB) rechallenge. METHODS: 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. RESULTS: Among 12 patients (52%) who experienced recurrent irAEs upon rechallenge, myocarditis recurrence occurred in 8 cases, with most (88%) presenting as grade 1- 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+ T cells with high TRAV19 expression (CD8 Teff TRAV19), a TCR Vα 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. CONCLUSION: 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.