{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T15:58:05Z","timestamp":1792166285893,"version":"4.4.0"},"reference-count":80,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T00:00:00Z","timestamp":1736812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Human natural killer (NK) cells can be sub-divided into two functional subsets but the clinical significance of these CD56<jats:sup>bright<\/jats:sup> and CD56<jats:sup>dim<\/jats:sup> NK cells in anti-tumour immunity remains largely unexplored. We determined the relative abundances of gene signatures for CD56<jats:sup>bright<\/jats:sup> and CD56<jats:sup>dim<\/jats:sup> NK cells along with 3 stromal and 18 other immune cell types in the patient tumour transcriptomes from the cancer genome atlas bladder cancer dataset (TCGA-BLCA). Using this computational approach, CD56<jats:sup>bright<\/jats:sup> NK cells were predicted to be the more abundant tumour-infiltrating NK subset which was also associated with improved patient prognosis. A similar favorable survival trend was projected using gene signatures for mature myeloid dendritic cells (mDC) and CD8<jats:sup>+<\/jats:sup> effector memory T cells (T<jats:sub>EM<\/jats:sub>) and unveiled a potential CD56<jats:sup>bright<\/jats:sup> NK-mDC-CD8<jats:sup>+<\/jats:sup>T cell crosstalk in the BLCA tumour microenvironment. Expression of transcripts encoding the activating NK cell receptors, NKG2D, NKp44, CD2, and CD160, showed positive survival trends in combination with CD56<jats:sup>bright<\/jats:sup> NK cell infiltration. Transcription factors including HOBIT, IRF3, and STAT2 were also correlated with CD56<jats:sup>bright<\/jats:sup> NK cell abundance. Additionally, a HOBIT-dependent tissue-residency program correlated with the CD56<jats:sup>bright<\/jats:sup> NK and CD8<jats:sup>+<\/jats:sup> T<jats:sub>EM<\/jats:sub> cell signatures was found to be associated with favourable BLCA patient survival. Overall, our study highlights the significance of CD56<jats:sup>bright<\/jats:sup> NK cells in BLCA patient prognosis. Our findings facilitate a better understanding of the NK cell anti-tumour responses that may ultimately lead to the development of promising NK and T cell-based therapies for BLCA.<\/jats:p>","DOI":"10.3389\/fimmu.2024.1474652","type":"journal-article","created":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T05:11:16Z","timestamp":1736831476000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Transcriptional signature of CD56bright NK cells predicts favourable prognosis in bladder cancer"],"prefix":"10.3389","volume":"15","author":[{"given":"Md Abdullah Al Kamran","family":"Khan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander James","family":"Sedgwick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhan","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian P.","family":"Vivian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra J.","family":"Corbett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Dolcetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theo","family":"Mantamadiotis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Mangiola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander David","family":"Barrow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,1,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA: A Cancer J Clin"},{"key":"B2","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1038\/s41571-023-00744-3","article-title":"Global trends in the epidemiology of bladder cancer: challenges for public health and clinical practice","volume":"20","author":"van Hoogstraten","year":"2023","journal-title":"Nat Rev Clin Oncol"},{"key":"B3","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-030-59038-3_17","article-title":"The tumor microenvironment of bladder cancer","volume-title":"Tumor microenvironments in organs: from the brain to the skin \u2013 part B","author":"Hatogai","year":"2020"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/nrurol.2014.15","article-title":"The mechanism of action of BCG therapy for bladder cancer\u2014a current perspective","volume":"11","author":"Redelman-Sidi","year":"2014","journal-title":"Nat Rev Urol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(17)30607-1","article-title":"De-novo and acquired resistance to immune checkpoint targeting","volume":"18","author":"Syn","year":"2017","journal-title":"Lancet Oncol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"55","DOI":"10.3390\/cancers11010055","article-title":"Exploiting NK cell surveillance pathways for cancer therapy","volume":"11","author":"Barrow","year":"2019","journal-title":"Cancers"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.a.v83a.8","article-title":"Human NK cell receptors\/markers: A tool to analyze NK cell development, subsets and function","author":"Montaldo","year":"2013","journal-title":"Cytometry Part A"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2008.03027.x","article-title":"CD56bright natural killer (NK) cells: an important NK cell subset","volume":"126","author":"Poli","year":"2009","journal-title":"Immunology"},{"key":"B9","first-page":"187","article-title":"Biology of natural killer cells","volume-title":"Advances in immunology","author":"Trinchieri","year":"1989"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2017.09.001","article-title":"Tailoring Natural Killer cell immunotherapy to the tumour microenvironment","volume":"31","author":"Barrow","year":"2017","journal-title":"Semin Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2006.06.013","article-title":"Human NK cell education by inhibitory receptors for MHC class I","volume":"25","author":"Anfossi","year":"2006","journal-title":"Immunity"},{"key":"B12","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1038\/s41571-020-0426-7","article-title":"Exploring the NK cell platform for cancer immunotherapy","volume":"18","author":"Myers","year":"2021","journal-title":"Nat Rev Clin Oncol"},{"key":"B13","first-page":"61","article-title":"Chapter Two - 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