Cardiac tertiary immune niches drive immune activation in immune checkpoint inhibitor myocarditis.
CC, T., M, P., S, B., X, H., R, W., & A, M. (2026). Cardiac tertiary immune niches drive immune activation in immune checkpoint inhibitor myocarditis.. Science advances. https://doi.org/10.1126/sciadv.aed8359
CC T, M P, S B, X H, R W, A M. Cardiac tertiary immune niches drive immune activation in immune checkpoint inhibitor myocarditis.. Science advances. 2026; doi: 10.1126/sciadv.aed8359
CC T, M P, S B, et al. Cardiac tertiary immune niches drive immune activation in immune checkpoint inhibitor myocarditis.[J]. Science advances. 2026. DOI: 10.1126/sciadv.aed8359.
@article{cc2026,
author = {Tymm CC and Paiola M and Bukhari S and Hu X and Winchester R and Mor A},
title = {Cardiac tertiary immune niches drive immune activation in immune checkpoint inhibitor myocarditis.},
journal = {Science advances},
year = {2026},
doi = {10.1126/sciadv.aed8359},
note = {PMID: 42647623},
}
TY - JOUR AU - Tymm CC AU - Paiola M AU - Bukhari S AU - Hu X AU - Winchester R AU - Mor A TI - Cardiac tertiary immune niches drive immune activation in immune checkpoint inhibitor myocarditis. T2 - Science advances PY - 2026 DO - 10.1126/sciadv.aed8359 AN - PMID:42647623 ER -
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+ monocytes and PD-1+ CD8+ 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.