{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T15:21:35Z","timestamp":1747149695993,"version":"3.40.5"},"reference-count":42,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,10,14]],"date-time":"2020-10-14T00:00:00Z","timestamp":1602633600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["eJHaem"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Follicular lymphoma (FL) is the most common indolent non\u2010Hodgkin lymphoma. Twenty to twenty\u2010five percent of FL patients have progression of disease within 24 months. These patients may benefit from immunotherapy if intact antigen presentation is present. Molecular mechanisms impairing major histocompatibility complex class\u2010I (MHC\u2010I) in FL remain undefined. Here, by sequencing of 172 FL tumours, we found the MHC\u2010I transactivator NLRC5 was the most frequent gene abnormality in the MHC\u2010I pathway. Pyrosequencing showed that epigenetic silencing of the<jats:italic>NLRC5<\/jats:italic>promoter occurred in 30% of cases and was mutually exclusive to copy number loss (CNL) in<jats:italic>NLRC5<\/jats:italic>(\u223c6% of cases). Hypermethylation and CNLs (\u201c<jats:italic>NLRC5<\/jats:italic>aberrant\u201d) had reduced<jats:italic>NLRC5<\/jats:italic>gene expression compared to wild\u2010type (WT) cases. By NanoString, there was reduced gene expression of the MHC\u2010I pathway in aberrant tissues, including immunoproteasome components (<jats:italic>PSMB8<\/jats:italic>and<jats:italic>PSMB9)<\/jats:italic>, peptide transporters of antigen processing (<jats:italic>TAP1<\/jats:italic>), and MHC\u2010I (<jats:italic>HLA\u2010A<\/jats:italic>), compared to WT. By immunofluorescent microscopy, fewer NLRC5 protein\u2010expressing malignant B\u2010cells were observed in NLRC5 aberrant tissue sections compared to NLRC5 WT (<jats:italic>P\u00a0<\/jats:italic>&lt;\u00a0.01). Consistent with a pivotal role in the activation of CD8<jats:sup>+<\/jats:sup>T\u2010cells, both<jats:italic>CD8<\/jats:italic>and<jats:italic>CD137<\/jats:italic>strongly correlated with NLRC5 expression (both<jats:italic>r\u00a0<\/jats:italic>&gt;\u00a00.7;<jats:italic>P\u00a0<\/jats:italic>&lt;\u00a0.0001). Further studies are required to determine whether patients with aberrant NLRC5 have a diminished response to immunotherapy.<\/jats:p>","DOI":"10.1002\/jha2.116","type":"journal-article","created":{"date-parts":[[2020,10,14]],"date-time":"2020-10-14T19:26:07Z","timestamp":1602703567000},"page":"517-526","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Genetic aberrations of<i>NLRC5<\/i>are associated with downregulated MHC\u2010I antigen presentation and impaired T\u2010cell immunity in follicular lymphoma"],"prefix":"10.1002","volume":"1","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2695-3849","authenticated-orcid":false,"given":"Jay","family":"Gunawardana","sequence":"first","affiliation":[{"name":"Mater Research University of Queensland, Translational Research Institute Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justina N.","family":"Lee","sequence":"additional","affiliation":[{"name":"Diamantina Institute University of Queensland Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7201-5269","authenticated-orcid":false,"given":"Karolina","family":"Bednarska","sequence":"additional","affiliation":[{"name":"Mater Research University of Queensland, Translational Research Institute Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentine","family":"Murigneux","sequence":"additional","affiliation":[{"name":"Diamantina Institute University of Queensland Brisbane Queensland Australia"},{"name":"QFAB Bioinformatics Institute for Molecular Bioscience University of Queensland Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lilia Merida","family":"de Long","sequence":"additional","affiliation":[{"name":"Mater Research University of Queensland, Translational Research Institute Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1977-8878","authenticated-orcid":false,"given":"Muhammed B.","family":"Sabdia","sequence":"additional","affiliation":[{"name":"Mater Research University of Queensland, Translational Research Institute Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone","family":"Birch","sequence":"additional","affiliation":[{"name":"Princess Alexandra Hospital Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua W. D.","family":"Tobin","sequence":"additional","affiliation":[{"name":"Mater Research University of Queensland, Translational Research Institute Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1000-5393","authenticated-orcid":false,"given":"Maher K.","family":"Gandhi","sequence":"additional","affiliation":[{"name":"Mater Research University of Queensland, Translational Research Institute Brisbane Queensland Australia"},{"name":"Princess Alexandra Hospital Brisbane Queensland Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,10,14]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"AIHW.Trends in the Incidence of Non\u2010Hodgkin Lymphoma.2017."},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-01-643569"},{"issue":"9","key":"e_1_2_9_4_1","doi-asserted-by":"crossref","first-page":"2146","DOI":"10.1002\/ijc.28849","article-title":"Lymphoid neoplasm incidence by WHO subtype in Australia 1982\u20132006","volume":"135","author":"Van Leeuwen MT","year":"2014","journal-title":"Int J Cancer"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3814"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI63186"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-03-491514"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.59.7534"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002197"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2016.205"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2017.127"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2403175"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.107522"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.08.032"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1501199112"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.10.008"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2008.273"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-230X(05)93006-6"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2011.11.006"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-18-1090"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3339"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2011.12.007"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1602069113"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.18.02365"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12716"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejh.13274"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.25306"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(15)00150-7"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-019-0109-9"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.02.013"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.021908.132715"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.01.040"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09754"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2013.12.027"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-2123"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-14-1860"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2016.09.010"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2012.56"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1102671"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2016.1151593"},{"key":"e_1_2_9_41_1","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s40425-016-0143-z","article-title":"NLRC5, a promising new entry in tumour immunology","volume":"4","author":"Chelbi ST","year":"2016","journal-title":"J Immunother Cancer"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-14-0983"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11899-018-0484-4"}],"container-title":["eJHaem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jha2.116","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jha2.116","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jha2.116","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T19:41:29Z","timestamp":1696880489000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jha2.116"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,14]]},"references-count":42,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,11]]}},"alternative-id":["10.1002\/jha2.116"],"URL":"https:\/\/doi.org\/10.1002\/jha2.116","archive":["Portico"],"relation":{},"ISSN":["2688-6146","2688-6146"],"issn-type":[{"type":"print","value":"2688-6146"},{"type":"electronic","value":"2688-6146"}],"subject":[],"published":{"date-parts":[[2020,10,14]]},"assertion":[{"value":"2020-08-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-10-03","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-10-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}