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 immun...
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doaj-6b326bb24b624e97b5dc1e2dce130e5f2021-05-11T14:48:14ZengNature Publishing GroupBlood Cancer Journal2044-53852021-05-011151910.1038/s41408-021-00477-5Distinct immune signatures in chronic lymphocytic leukemia and Richter syndromeYucai Wang0Sutapa Sinha1Linda E. Wellik2Charla R. Secreto3Karen L. Rech4Timothy G. Call5Sameer A. Parikh6Saad S. Kenderian7Eli Muchtar8Suzanne R. Hayman9Amber B. Koehler10Daniel L. Van Dyke11Jose F. Leis12Susan L. Slager13Haidong Dong14Neil E. Kay15Rong He16Wei Ding17Division of Hematology, Mayo ClinicDivision of Hematology, Mayo ClinicDivision of Hematology, Mayo ClinicDivision of Hematology, Mayo ClinicDivision of Hematopathology, Mayo ClinicDivision of Hematology, Mayo ClinicDivision of Hematology, Mayo ClinicDivision of Hematology, Mayo ClinicDivision of Hematology, Mayo ClinicDivision of Hematology, Mayo ClinicDivision of Hematology, Mayo ClinicDivision of Laboratory Genetics and Genomics, Mayo ClinicDivision of Hematology and Medical Oncology, Mayo ClinicDivision of Biomedical Statistics and Informatics, Mayo ClinicDepartment of Immunology, Mayo ClinicDivision of Hematology, Mayo ClinicDivision of Hematopathology, Mayo ClinicDivision of Hematology, Mayo ClinicAbstract 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.https://doi.org/10.1038/s41408-021-00477-5 |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yucai Wang Sutapa Sinha Linda E. Wellik Charla R. Secreto Karen L. Rech Timothy G. Call Sameer A. Parikh Saad S. Kenderian Eli Muchtar Suzanne R. Hayman Amber B. Koehler Daniel L. Van Dyke Jose F. Leis Susan L. Slager Haidong Dong Neil E. Kay Rong He Wei Ding |
spellingShingle |
Yucai Wang Sutapa Sinha Linda E. Wellik Charla R. Secreto Karen L. Rech Timothy G. Call Sameer A. Parikh Saad S. Kenderian Eli Muchtar Suzanne R. Hayman Amber B. Koehler Daniel L. Van Dyke Jose F. Leis Susan L. Slager Haidong Dong Neil E. Kay Rong He Wei Ding Distinct immune signatures in chronic lymphocytic leukemia and Richter syndrome Blood Cancer Journal |
author_facet |
Yucai Wang Sutapa Sinha Linda E. Wellik Charla R. Secreto Karen L. Rech Timothy G. Call Sameer A. Parikh Saad S. Kenderian Eli Muchtar Suzanne R. Hayman Amber B. Koehler Daniel L. Van Dyke Jose F. Leis Susan L. Slager Haidong Dong Neil E. Kay Rong He Wei Ding |
author_sort |
Yucai Wang |
title |
Distinct immune signatures in chronic lymphocytic leukemia and Richter syndrome |
title_short |
Distinct immune signatures in chronic lymphocytic leukemia and Richter syndrome |
title_full |
Distinct immune signatures in chronic lymphocytic leukemia and Richter syndrome |
title_fullStr |
Distinct immune signatures in chronic lymphocytic leukemia and Richter syndrome |
title_full_unstemmed |
Distinct immune signatures in chronic lymphocytic leukemia and Richter syndrome |
title_sort |
distinct immune signatures in chronic lymphocytic leukemia and richter syndrome |
publisher |
Nature Publishing Group |
series |
Blood Cancer Journal |
issn |
2044-5385 |
publishDate |
2021-05-01 |
description |
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. |
url |
https://doi.org/10.1038/s41408-021-00477-5 |
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