Matches in SemOpenAlex for { <https://semopenalex.org/work/W2964133630> ?p ?o ?g. }
- W2964133630 endingPage "1250" @default.
- W2964133630 startingPage "1243" @default.
- W2964133630 abstract "Checkpoint inhibitors produce durable responses in numerous metastatic cancers, but immune-related adverse events (irAEs) complicate and limit their benefit. IrAEs can affect organ systems idiosyncratically; presentations range from mild and self-limited to fulminant and fatal. The molecular mechanisms underlying irAEs are poorly understood. Here, we report a fatal case of encephalitis arising during anti-programmed cell death receptor 1 therapy in a patient with metastatic melanoma. Histologic analyses revealed robust T cell infiltration and prominent programmed death ligand 1 expression. We identified 209 reported cases in global pharmacovigilance databases (across multiple cancer types) of encephalitis associated with checkpoint inhibitor regimens, with a 19% fatality rate. We performed further analyses from the index case and two additional cases to shed light on this recurrent and fulminant irAE. Spatial and multi-omic analyses pinpointed activated memory CD4+ T cells as highly enriched in the inflamed, affected region. We identified a highly oligoclonal T cell receptor repertoire, which we localized to activated memory cytotoxic (CD45RO+GZMB+Ki67+) CD4 cells. We also identified Epstein-Barr virus-specific T cell receptors and EBV+ lymphocytes in the affected region, which we speculate contributed to neural inflammation in the index case. Collectively, the three cases studied here identify CD4+ and CD8+ T cells as culprits of checkpoint inhibitor-associated immune encephalitis." @default.
- W2964133630 created "2019-07-30" @default.
- W2964133630 creator A5008000580 @default.
- W2964133630 creator A5012138398 @default.
- W2964133630 creator A5014313539 @default.
- W2964133630 creator A5016502031 @default.
- W2964133630 creator A5017831693 @default.
- W2964133630 creator A5019401898 @default.
- W2964133630 creator A5022520811 @default.
- W2964133630 creator A5025067315 @default.
- W2964133630 creator A5025670257 @default.
- W2964133630 creator A5030009480 @default.
- W2964133630 creator A5030367169 @default.
- W2964133630 creator A5035539932 @default.
- W2964133630 creator A5037252693 @default.
- W2964133630 creator A5046320640 @default.
- W2964133630 creator A5055600535 @default.
- W2964133630 creator A5055625321 @default.
- W2964133630 creator A5055897523 @default.
- W2964133630 creator A5059525044 @default.
- W2964133630 creator A5063177685 @default.
- W2964133630 creator A5065304569 @default.
- W2964133630 creator A5066489948 @default.
- W2964133630 creator A5067316056 @default.
- W2964133630 creator A5070065201 @default.
- W2964133630 creator A5070165631 @default.
- W2964133630 creator A5071577704 @default.
- W2964133630 creator A5075566772 @default.
- W2964133630 creator A5079594267 @default.
- W2964133630 creator A5081827829 @default.
- W2964133630 creator A5082913203 @default.
- W2964133630 creator A5086895898 @default.
- W2964133630 creator A5089113899 @default.
- W2964133630 creator A5089223773 @default.
- W2964133630 creator A5090648125 @default.
- W2964133630 date "2019-07-22" @default.
- W2964133630 modified "2023-10-13" @default.
- W2964133630 title "A case report of clonal EBV-like memory CD4+ T cell activation in fatal checkpoint inhibitor-induced encephalitis" @default.
- W2964133630 cites W1584625860 @default.
- W2964133630 cites W1595660380 @default.
- W2964133630 cites W1648161244 @default.
- W2964133630 cites W1985987855 @default.
- W2964133630 cites W1999574084 @default.
- W2964133630 cites W2010857492 @default.
- W2964133630 cites W2039123767 @default.
- W2964133630 cites W2042150163 @default.
- W2964133630 cites W2050986039 @default.
- W2964133630 cites W2068845968 @default.
- W2964133630 cites W2085247907 @default.
- W2964133630 cites W2121723772 @default.
- W2964133630 cites W2130579933 @default.
- W2964133630 cites W2137586531 @default.
- W2964133630 cites W2165229668 @default.
- W2964133630 cites W2169456326 @default.
- W2964133630 cites W2172071135 @default.
- W2964133630 cites W2185265351 @default.
- W2964133630 cites W2227062383 @default.
- W2964133630 cites W2275606382 @default.
- W2964133630 cites W2522337762 @default.
- W2964133630 cites W2523044687 @default.
- W2964133630 cites W2537525060 @default.
- W2964133630 cites W2547133566 @default.
- W2964133630 cites W2551653151 @default.
- W2964133630 cites W2561156916 @default.
- W2964133630 cites W2562254730 @default.
- W2964133630 cites W2589191322 @default.
- W2964133630 cites W2607237575 @default.
- W2964133630 cites W2612010935 @default.
- W2964133630 cites W2613978126 @default.
- W2964133630 cites W2620061050 @default.
- W2964133630 cites W2670890989 @default.
- W2964133630 cites W2671261300 @default.
- W2964133630 cites W2752126733 @default.
- W2964133630 cites W2754887039 @default.
- W2964133630 cites W2781484625 @default.
- W2964133630 cites W2783137027 @default.
- W2964133630 cites W2784031161 @default.
- W2964133630 cites W2793167197 @default.
- W2964133630 cites W2891486030 @default.
- W2964133630 cites W2895125473 @default.
- W2964133630 cites W2903686952 @default.
- W2964133630 cites W3105082142 @default.
- W2964133630 doi "https://doi.org/10.1038/s41591-019-0523-2" @default.
- W2964133630 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6689251" @default.
- W2964133630 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/31332390" @default.
- W2964133630 hasPublicationYear "2019" @default.
- W2964133630 type Work @default.
- W2964133630 sameAs 2964133630 @default.
- W2964133630 citedByCount "126" @default.
- W2964133630 countsByYear W29641336302019 @default.
- W2964133630 countsByYear W29641336302020 @default.
- W2964133630 countsByYear W29641336302021 @default.
- W2964133630 countsByYear W29641336302022 @default.
- W2964133630 countsByYear W29641336302023 @default.
- W2964133630 crossrefType "journal-article" @default.
- W2964133630 hasAuthorship W2964133630A5008000580 @default.
- W2964133630 hasAuthorship W2964133630A5012138398 @default.
- W2964133630 hasAuthorship W2964133630A5014313539 @default.