@article{95c747d2483d40ce975d4925dbb58e83,
title = "Distinct immune signatures in chronic lymphocytic leukemia and Richter syndrome",
abstract = "Richter syndrome (RS) refers to transformation of chronic lymphocytic leukemia (CLL) to an aggressive lymphoma, most commonly diffuse large B-cell lymphoma. RS is known to be associated with a number of genetic alterations such as TP53 and NOTCH1 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%, P < 0.01) and PD1 expression in neoplastic B cells (median 26.0% vs. 6.2%, P < 0.01), and higher infiltration of FOXP3-positive T cells (median 1.7% vs. 0.4%, P < 0.01) and CD163-positive macrophages (median 23.4% vs. 9.1%, P < 0.01). In addition, peripheral blood T-cell receptor clonality was significantly lower in RS vs. CLL patients (median [25th–75th], 0.107 [0.070–0.209] vs. 0.233 [0.111–0.406], P = 0.046), 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.",
author = "Yucai Wang and Sutapa Sinha and Wellik, {Linda E.} and Secreto, {Charla R.} and Rech, {Karen L.} and Call, {Timothy G.} and Parikh, {Sameer A.} and Kenderian, {Saad S.} and Eli Muchtar and Hayman, {Suzanne R.} and Koehler, {Amber B.} and {Van Dyke}, {Daniel L.} and Leis, {Jose F.} and Slager, {Susan L.} and Haidong Dong and Kay, {Neil E.} and Rong He and Wei Ding",
note = "Funding Information: This study is partially funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. S.A.P. and S.S.K. are recipients of the K12 CA090628 Grant from the National Cancer Institute (Paul Calabresi Career Development Award for Clinical Oncology). S.A.P. acknowledges support from the Mayo Clinic K2R Career Development Program. Funding Information: Y.W. reports research funding (provided to the institution) from Incyte, InnoCare, Novartis, and Genentech. 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). Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = may,
doi = "10.1038/s41408-021-00477-5",
language = "English (US)",
volume = "11",
journal = "Blood cancer journal",
issn = "2044-5385",
publisher = "Nature Publishing Group",
number = "5",
}