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RS is known to be associated with a number of genetic alterations such as<jats:italic>TP53<\/jats:italic>and<jats:italic>NOTCH1<\/jats:italic>mutations. However, it is unclear what immune microenvironment changes are associated with RS. In this study, we analyzed expression of immune checkpoint molecules and infiltration of immune cells in nodal samples, and peripheral blood T-cell diversity in 33 CLL and 37 RS patients. Compared to CLL, RS nodal tissue had higher PD-L1 expression in histiocytes and dendritic cells (median 16.6% vs. 2.8%,<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01) and PD1 expression in neoplastic B cells (median 26.0% vs. 6.2%,<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01), and higher infiltration of FOXP3-positive T cells (median 1.7% vs. 0.4%,<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01) and CD163-positive macrophages (median 23.4% vs. 9.1%,<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.01). In addition, peripheral blood T-cell receptor clonality was significantly lower in RS vs. CLL patients (median [25th\u201375th], 0.107 [0.070\u20130.209] vs. 0.233 [0.111\u20130.406],<jats:italic>P<\/jats:italic>\u2009=\u20090.046), suggesting that T cells in RS patients were significantly more diverse than in CLL patients. Collectively these data suggest that CLL and RS have distinct immune signatures. Better understanding of the immune microenvironment is essential to improve immunotherapy efficacy in CLL and RS.<\/jats:p>","DOI":"10.1038\/s41408-021-00477-5","type":"journal-article","created":{"date-parts":[[2021,5,10]],"date-time":"2021-05-10T11:05:51Z","timestamp":1620644751000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Distinct immune signatures in chronic lymphocytic leukemia and Richter syndrome"],"prefix":"10.1038","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1576-8341","authenticated-orcid":false,"given":"Yucai","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sutapa","family":"Sinha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda E.","family":"Wellik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charla R.","family":"Secreto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen L.","family":"Rech","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy G.","family":"Call","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3221-7314","authenticated-orcid":false,"given":"Sameer A.","family":"Parikh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2767-3830","authenticated-orcid":false,"given":"Saad S.","family":"Kenderian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eli","family":"Muchtar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suzanne R.","family":"Hayman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amber B.","family":"Koehler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel L.","family":"Van Dyke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jose F.","family":"Leis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan L.","family":"Slager","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haidong","family":"Dong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5951-5055","authenticated-orcid":false,"given":"Neil E.","family":"Kay","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rong","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9811-4601","authenticated-orcid":false,"given":"Wei","family":"Ding","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,5,10]]},"reference":[{"key":"477_CR1","doi-asserted-by":"publisher","first-page":"684","DOI":"10.1038\/s41571-019-0239-8","volume":"16","author":"F Bosch","year":"2019","unstructured":"Bosch, F. & Dalla-Favera, R. 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S.A.P. reports funding (provided to the institution) from Pharmacyclics, Janssen, AstraZeneca, TG Therapeutics, Merck, AbbVie, and Ascentage Pharma for clinical studies in which he is a principal investigator, and participation in advisory board meetings of Pharmacyclics, AstraZeneca, Genentech, Gilead, GlaxoSmithKline, Verastem Oncology, and AbbVie (he was not personally compensated). S.S.K. acknowledges patents and royalties to Novartis, Humanigen, and Mettaforge, research funding from Kite, Gilead, Juno, Celegene, Novartis, Toledo, Humanigen, Lentigen, Morphosys, and Sunesis, and advisory board membership for Kite, Humanigen, and Juno. N.E.K. reports research funding from AbbVie, Acerta Pharma, Bristol Meyer Squibb, Celgene, MEI Pharma, Pharmacyclics, Sunesis, TG Therapeutics, Tolero Pharmaceuticals, data safety monitoring committee for Agios Pharm, AstraZeneca, Bristol Meyer Squibb-Celgene, Cytomx Therapeutics, MorphoSys, Rigel, and advisory board for AbbVie, AstraZeneca, Cytomx Therapy, Dava Oncology, Juno Therapeutics, Oncotracker, Pharmacyclics. W.D. reports research funding (provided to the institution) from Merck and DTRM, and participation in advisory board meetings of Octapharma and Alexion (she was not personally compensated).","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"86"}}