{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T08:54:27Z","timestamp":1771059267579,"version":"3.50.1"},"reference-count":25,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,8,23]],"date-time":"2021-08-23T00:00:00Z","timestamp":1629676800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Richter syndrome (RS), an aggressive lymphoma occurring in the context of chronic lymphocytic leukaemia\/small lymphocytic lymphoma, is associated with poor prognosis when treated with conventional immunochemotherapy, therefore, improved treatments are required. Immune checkpoint blockade has shown efficacy in some B\u2010cell malignancies and modest responses in early clinical trials for RS. We investigated the immune checkpoint profile of RS as a basis to inform rational therapeutic investigations in RS.<\/jats:p><jats:p>Formalin\u2010fixed, paraffin\u2010embedded biopsies of RS (<jats:italic>n<\/jats:italic>\u00a0=\u00a019), <jats:italic>de novo<\/jats:italic> diffuse large B\u2010cell lymphoma (DLBCL; <jats:italic>n<\/jats:italic>\u00a0=\u00a058), transformed indolent lymphomas (follicular [tFL], <jats:italic>n<\/jats:italic>\u00a0=\u00a016; marginal zone [tMZL], <jats:italic>n<\/jats:italic>\u00a0=\u00a024) and non\u2010transformed small lymphocytic lymphoma (SLL; <jats:italic>n<\/jats:italic>\u00a0=\u00a015) underwent gene expression profiling using the NanoString Human Immunology panel. Copy number assessment was performed using next\u2010generation sequencing. Immunohistochemistry (IHC) for LAG3 and PD\u20101 was performed.<\/jats:p><jats:p><jats:italic>LAG3<\/jats:italic> gene expression was higher in RS compared to DLBCL (<jats:italic>P<\/jats:italic>\u00a0=\u00a00\u00b70002, log2FC 1\u00b796), tFL (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00\u00b70001, log2FC 2\u00b761), tMZL (<jats:italic>P<\/jats:italic>\u00a0=\u00a00\u00b70004, log2FC 1\u00b779) and SLL (<jats:italic>P<\/jats:italic>\u00a0=\u00a00\u00b70057, log2FC 1\u00b745). <jats:italic>LAG3<\/jats:italic> gene expression correlated with the gene expression of human leukocyte antigen Class I and II, and related immune genes and immune checkpoints. IHC revealed LAG3 protein expression on both malignant RS cells and tumour\u2010infiltrating lymphocytes. Our findings support the investigation of LAG3 inhibition to enhance anti\u2010tumour responses in RS.<\/jats:p>","DOI":"10.1111\/bjh.17789","type":"journal-article","created":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T06:06:57Z","timestamp":1629785217000},"page":"113-118","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Characterisation of immune checkpoints in Richter syndrome identifies LAG3 as a potential therapeutic target"],"prefix":"10.1111","volume":"195","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3043-9503","authenticated-orcid":false,"given":"Clare","family":"Gould","sequence":"first","affiliation":[{"name":"Pathology Department Peter MacCallum Cancer Centre Melbourne Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Lickiss","sequence":"additional","affiliation":[{"name":"Pathology Department Peter MacCallum Cancer Centre Melbourne 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