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.