Immune responses in checkpoint myocarditis across heart, blood and tumour

@ARTICLE{Blum2024-qd,
  title     = "{Immune responses in checkpoint myocarditis across heart, blood
               and tumour}",
  author    = "Blum, Steven M and Zlotoff, Daniel A and Smith, Neal P and
               Kernin, Isabela J and Ramesh, Swetha and Zubiri, Leyre and
               Caplin, Joshua and Samanta, Nandini and Martin, Sidney and Wang,
               Mike and Tirard, Alice and Song, Yuhui and Xu, Katherine H and
               Barth, Jaimie and Sen, Pritha and Slowikowski, Kamil and
               Tantivit, Jessica and Manakongtreecheep, Kasidet and Arnold,
               Benjamin Y and Nasrallah, Mazen and Pinto, Christopher J and
               McLoughlin, Daniel and Jackson, Monica and Chan, Puiyee and
               Lawless, Aleigha and Michaud, William A and Sharova, Tatyana and
               Nieman, Linda T and Gainor, Justin F and Wu, Catherine J and
               Juric, Dejan and Mino-Kenudson, Mari and Oliveira, Giacomo and
               Sullivan, Ryan J and Boland, Genevieve M and Stone, James R and
               Thomas, Molly F and Neilan, Tomas G and Reynolds, Kerry L and
               Villani, Alexandra-Chloé",
  journal   = "Nature",
  publisher = "Nature Publishing Group",
  pages     = "1--9",
  abstract  = "Immune checkpoint inhibitors are widely used anticancer
               therapies1 that can cause morbid and potentially fatal
               immune-related adverse events such as immune-related myocarditis
               (irMyocarditis)2–5. The pathogenesis of irMyocarditis and its
               relationship to antitumour immunity remain poorly understood.
               Here we sought to define immune responses in heart, tumour and
               blood in patients with irMyocarditis by leveraging single-cell
               RNA sequencing coupled with T cell receptor (TCR) sequencing,
               microscopy and proteomics analyses of samples from 28 patients
               with irMyocarditis and 41 unaffected individuals. Analyses of
               84,576 cardiac cells by single-cell RNA sequencing combined with
               multiplexed microscopy demonstrated increased frequencies and
               co-localization of cytotoxic T cells, conventional dendritic
               cells and inflammatory fibroblasts in irMyocarditis heart tissue.
               Analyses of 366,066 blood cells revealed decreased frequencies of
               plasmacytoid dendritic cells, conventional dendritic cells and B
               lineage cells but an increased frequency of other mononuclear
               phagocytes in irMyocarditis. Fifty-two heart-expanded TCR clones
               from eight patients did not recognize the putative cardiac
               autoantigens α-myosin, troponin I or troponin T. Additionally,
               TCRs enriched in heart tissue were largely nonoverlapping with
               those enriched in paired tumour tissue. The presence of
               heart-expanded TCRs in a cycling blood CD8 T cell population was
               associated with fatal irMyocarditis case status. Collectively,
               these findings highlight crucial biology driving irMyocarditis
               and identify putative biomarkers. The molecular characteristics
               of myocarditis associated with immune checkpoint inhibitors are
               described and potential biomarkers of onset and severity are
               identified.",
  month     =  nov,
  year      =  2024,
  doi       = "10.1038/s41586-024-08105-5",
  issn      = "0028-0836,1476-4687",
  language  = "en"
}