{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:59:05Z","timestamp":1791475145395,"version":"4.3.4"},"reference-count":44,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T00:00:00Z","timestamp":1654041600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Kinderkrebsinitiative Buchholz, HolmSeppensen (KKI)","award":["project B9"],"award-info":[{"award-number":["project B9"]}]},{"name":"DFG via SFB1074","award":["project B9"],"award-info":[{"award-number":["project B9"]}]},{"name":"The Seed Funding initiative of the medical faculty of the University of Kiel","award":["project B9"],"award-info":[{"award-number":["project B9"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ncRNA"],"abstract":"<jats:p>Successful immunotherapy in both solid tumors and in hematological malignancies relies on the ability of T lymphocytes to infiltrate the cancer tissue and mount an immune response against the tumor. Biomarkers able to discern the amount and the types of T lymphocytes infiltrating a given tumor therefore have high diagnostic and prognostic value. Given that lncRNAs are known to have a highly cell-type-specific expression pattern, we searched for lncRNAs specifically expressed by activated T cells and at the same time in a kind of lymphoma, follicular lymphoma, where the microenvironment is known to play a critical role in the regulation of antitumor immunity. We focused on a non-coding transcript, annotated as LINC00892, which reaches extremely high expression levels following cell activation in Jurkat cells. Interestingly LINC00892 has an expression pattern resembling that of genes involved in T cell memory. Accordingly, LINC00892 is mostly expressed by the effector memory and helper CD4+ T cell sub-types but not by na\u00efve T cells. In situ analyses of LINC00892 expression in normal lymph nodes and in follicular lymphoma biopsies show that its expression is limited to CD4+ PD1hi T cells, with a subcellular localization within the germinal center matching that of follicular helper T cells. Our analysis therefore suggests that the previously uncharacterized lncRNA LINC00892 could be a useful biomarker for the detection of CD4+ memory T cells in both normal and tumor tissues.<\/jats:p>","DOI":"10.3390\/ncrna8030040","type":"journal-article","created":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T03:33:18Z","timestamp":1654054398000},"page":"40","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["LINC00892 Is an lncRNA Induced by T Cell Activation and Expressed by Follicular Lymphoma-Resident T Helper Cells"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7324-993X","authenticated-orcid":false,"given":"Ingram","family":"Iaccarino","sequence":"first","affiliation":[{"name":"Department of Pathology, Hematopathology Section and Lymph Node Registry, University of Kiel, 24105 Kiel, Germany"},{"name":"Institute of Genetics and Biophysics \u201cA. Buzzati-Traverso\u201d, Consiglio Nazionale delle Ricerche, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatme","family":"Mourtada","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hematopathology Section and Lymph Node Registry, University of Kiel, 24105 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9729-4030","authenticated-orcid":false,"given":"Sarah","family":"Reinke","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hematopathology Section and Lymph Node Registry, University of Kiel, 24105 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paurnima","family":"Patil","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Ulm University, Ulm University Medical Center, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gero","family":"Doose","sequence":"additional","affiliation":[{"name":"ecSeq Bioinformatics GmbH, 04103 Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianni","family":"Monaco","sequence":"additional","affiliation":[{"name":"Institute for Transfusion Medicine and Gene Therapy, Medical Center\u2014University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Leibniz Institute on Aging\u2014Fritz Lipmann Institute (FLI), 07745 Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reiner","family":"Siebert","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Ulm University, Ulm University Medical Center, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfram","family":"Klapper","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hematopathology Section and Lymph Node Registry, University of Kiel, 24105 Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2259","DOI":"10.2174\/138920112802501999","article-title":"The tumor stroma as mediator of drug resistance--a potential target to improve cancer therapy?","volume":"13","author":"Sebens","year":"2012","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.ccr.2012.02.022","article-title":"Accessories to the crime: Functions of cells recruited to the tumor microenvironment","volume":"21","author":"Hanahan","year":"2012","journal-title":"Cancer Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1038\/nrc3239","article-title":"The blockade of immune checkpoints in cancer immunotherapy","volume":"12","author":"Pardoll","year":"2012","journal-title":"Nat. Rev. Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1038\/nrc3245","article-title":"The immune contexture in human tumours: Impact on clinical outcome","volume":"12","author":"Fridman","year":"2012","journal-title":"Nat. Rev. Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1038\/s41571-019-0175-7","article-title":"Regulatory T cells in cancer immunosuppression\u2014Implications for anticancer therapy","volume":"16","author":"Togashi","year":"2019","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.1056\/NEJMoa041869","article-title":"Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells","volume":"351","author":"Dave","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6358","DOI":"10.1200\/JCO.2005.26.856","article-title":"Molecular pathogenesis of follicular lymphoma: A cross talk of genetic and immunologic factors","volume":"23","year":"2005","journal-title":"J. Clin. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1053\/j.semdp.2011.02.006","article-title":"Pathobiology and diagnosis of follicular lymphoma","volume":"28","author":"Klapper","year":"2011","journal-title":"Semin. Diagn. Pathol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"5350","DOI":"10.1200\/JCO.2006.06.4766","article-title":"Immunohistochemical patterns of reactive microenvironment are associated with clinicobiologic behavior in follicular lymphoma patients","volume":"24","author":"Alvaro","year":"2006","journal-title":"J. Clin. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1200\/JCO.2006.06.1648","article-title":"Gene-expression and immunohistochemical study of specific T-cell subsets and accessory cell types in the transformation and prognosis of follicular lymphoma","volume":"25","author":"Glas","year":"2007","journal-title":"J. Clin. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1200\/JCO.2008.18.0513","article-title":"High numbers of tumor-infiltrating programmed cell death 1-positive regulatory lymphocytes are associated with improved overall survival in follicular lymphoma","volume":"27","author":"Carreras","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1007\/s12307-018-0217-1","article-title":"T-cell clustering in neoplastic follicles of follicular lymphoma","volume":"11","author":"Schnotalle","year":"2018","journal-title":"Cancer Microenviron."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2178","DOI":"10.1016\/j.celrep.2019.01.085","article-title":"Mass cytometry analysis reveals that specific intratumoral CD4(+) T cell subsets correlate with patient survival in follicular lymphoma","volume":"26","author":"Yang","year":"2019","journal-title":"Cell Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1146\/annurev-biochem-051410-092902","article-title":"Genome regulation by long noncoding RNAs","volume":"81","author":"Rinn","year":"2012","journal-title":"Annu. Rev. Biochem."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Iaccarino, I. (2017). lncRNAs and MYC: An intricate relationship. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18071497"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.cell.2018.01.011","article-title":"Functional classification and experimental dissection of long noncoding RNAs","volume":"172","author":"Kopp","year":"2018","journal-title":"Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1101\/gad.17446611","article-title":"Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses","volume":"25","author":"Cabili","year":"2011","journal-title":"Genes Dev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1101\/gr.132159.111","article-title":"The GENCODE v7 catalog of human long noncoding RNAs: Analysis of their gene structure, evolution, and expression","volume":"22","author":"Derrien","year":"2012","journal-title":"Genome Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/nature11233","article-title":"Landscape of transcription in human cells","volume":"489","author":"Djebali","year":"2012","journal-title":"Nature"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1038\/nbt.1914","article-title":"Transcriptome sequencing across a prostate cancer cohort identifies PCAT-1, an unannotated lincRNA implicated in disease progression","volume":"29","author":"Prensner","year":"2011","journal-title":"Nat. Biotechnol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"E5261","DOI":"10.1073\/pnas.1505753112","article-title":"MINCR is a MYC-induced lncRNA able to modulate MYC\u2019s transcriptional network in Burkitt lymphoma cells","volume":"112","author":"Doose","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/978-1-0716-1581-2_2","article-title":"LncRNA as cancer biomarkers","volume":"2348","author":"Iaccarino","year":"2021","journal-title":"Methods Mol. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2002","DOI":"10.1038\/s41375-021-01251-z","article-title":"Mutational mechanisms shaping the coding and noncoding genome of germinal center derived B-cell lymphomas","volume":"35","author":"Hubschmann","year":"2021","journal-title":"Leukemia"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1038\/s41467-019-08578-3","article-title":"Genomic and transcriptomic changes complement each other in the pathogenesis of sporadic Burkitt lymphoma","volume":"10","author":"Lopez","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1038\/nri1330","article-title":"Jurkat T cells and development of the T-cell receptor signalling paradigm","volume":"4","author":"Abraham","year":"2004","journal-title":"Nat. Rev. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2448","DOI":"10.1242\/jcs.181248","article-title":"Nuclear PKC-theta facilitates rapid transcriptional responses in human memory CD4+ T cells through p65 and H2B phosphorylation","volume":"129","author":"Li","year":"2016","journal-title":"J. Cell Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"44825","DOI":"10.1038\/srep44825","article-title":"Priming of transcriptional memory responses via the chromatin accessibility landscape in T cells","volume":"7","author":"Tu","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"531","DOI":"10.3324\/haematol.2015.139493","article-title":"Role of the tumor microenvironment in mature B-cell lymphoid malignancies","volume":"101","author":"Fowler","year":"2016","journal-title":"Haematologica"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1038\/s41588-019-0505-9","article-title":"Landscape of stimulation-responsive chromatin across diverse human immune cells","volume":"51","author":"Calderon","year":"2019","journal-title":"Nat. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"60155","DOI":"10.18632\/oncotarget.11165","article-title":"The miR-223 host non-coding transcript linc-223 induces IRF4 expression in acute myeloid leukemia by acting as a competing endogenous RNA","volume":"7","author":"Mangiavacchi","year":"2016","journal-title":"Oncotarget"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1016\/j.celrep.2019.01.041","article-title":"RNA-Seq signatures normalized by mRNA abundance allow absolute deconvolution of human immune cell types","volume":"26","author":"Monaco","year":"2019","journal-title":"Cell Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.tig.2014.01.004","article-title":"The four dimensions of noncoding RNA conservation","volume":"30","author":"Diederichs","year":"2014","journal-title":"Trends Genet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e01749","DOI":"10.7554\/eLife.01749","article-title":"Multiple knockout mouse models reveal lincRNAs are required for life and brain development","volume":"2","author":"Sauvageau","year":"2013","journal-title":"Elife"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.ygeno.2012.07.014","article-title":"Discovery and characterization of new transcripts from RNA-seq data in mouse CD4 (+) T cells","volume":"100","author":"Hutchins","year":"2012","journal-title":"Genomics"},{"key":"ref_35","unstructured":"The ICGC\/TCGA Pan-Cancer Analysis of Whole Genomes Consortium (2020). Pan-cancer analysis of whole genomes. Nature, 578, 82\u201393."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.jmoldx.2011.08.002","article-title":"RNAscope: A novel in situ RNA analysis platform for formalin-fixed, paraffin-embedded tissues","volume":"14","author":"Wang","year":"2012","journal-title":"J. Mol. Diagn."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1084\/jem.180.4.1251","article-title":"Heterogeneity of single cell cytokine gene expression in clonal T cell populations","volume":"180","author":"Bucy","year":"1994","journal-title":"J. Exp. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2652","DOI":"10.4049\/jimmunol.1602033","article-title":"Integration of kinase and calcium signaling at the level of chromatin underlies inducible gene activation in T cells","volume":"199","author":"Brignall","year":"2017","journal-title":"J. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"33926","DOI":"10.1074\/jbc.M505748200","article-title":"Phorbol ester-induced G1 phase arrest selectively mediated by protein kinase Cdelta-dependent induction of p21","volume":"280","author":"Nakagawa","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1111\/j.1600-065X.2009.00782.x","article-title":"Molecular mechanism and function of CD40\/CD40L engagement in the immune system","volume":"229","author":"Elgueta","year":"2009","journal-title":"Immunol. Rev."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1016\/j.celrep.2018.10.027","article-title":"Genetic models reveal cis and trans immune-regulatory activities for lincRNA-Cox2","volume":"25","author":"Elling","year":"2018","journal-title":"Cell Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e68","DOI":"10.1182\/blood-2013-02-486944","article-title":"The enhancer and promoter landscape of human regulatory and conventional T-cell subpopulations","volume":"123","author":"Schmidl","year":"2014","journal-title":"Blood"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"W537","DOI":"10.1093\/nar\/gky379","article-title":"The galaxy platform for accessible, reproducible and collaborative biomedical analyses: 2018 update","volume":"46","author":"Afgan","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"12648","DOI":"10.1038\/s41598-018-31154-6","article-title":"Instant clue: A software suite for interactive data visualization and analysis","volume":"8","author":"Nolte","year":"2018","journal-title":"Sci. Rep."}],"container-title":["Non-Coding RNA"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2311-553X\/8\/3\/40\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:23:10Z","timestamp":1760138590000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2311-553X\/8\/3\/40"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,1]]},"references-count":44,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["ncrna8030040"],"URL":"https:\/\/doi.org\/10.3390\/ncrna8030040","relation":{},"ISSN":["2311-553X"],"issn-type":[{"value":"2311-553X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,1]]}}}