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Distinct immune composition in lymph node and peripheral blood of CLL patients is reshaped during venetoclax treatment

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Harvard

de Weerdt, I, Hofland, T, de Boer, R, Dobber, JA, Dubois, J, van Nieuwenhuize, D, Mobasher, M, de Boer, F, Hoogendoorn, M, Velders, GA, van der Klift, M, Remmerswaal, EBM, Bemelman, FJ, Niemann, CU, Kersting, S, Levin, M-D, Eldering, E, Tonino, SH & Kater, AP 2019, 'Distinct immune composition in lymph node and peripheral blood of CLL patients is reshaped during venetoclax treatment' Blood advances, bind 3, nr. 17, s. 2642-2652. https://doi.org/10.1182/bloodadvances.2019000360

APA

de Weerdt, I., Hofland, T., de Boer, R., Dobber, J. A., Dubois, J., van Nieuwenhuize, D., ... Kater, A. P. (2019). Distinct immune composition in lymph node and peripheral blood of CLL patients is reshaped during venetoclax treatment. Blood advances, 3(17), 2642-2652. https://doi.org/10.1182/bloodadvances.2019000360

CBE

de Weerdt I, Hofland T, de Boer R, Dobber JA, Dubois J, van Nieuwenhuize D, Mobasher M, de Boer F, Hoogendoorn M, Velders GA, van der Klift M, Remmerswaal EBM, Bemelman FJ, Niemann CU, Kersting S, Levin M-D, Eldering E, Tonino SH, Kater AP. 2019. Distinct immune composition in lymph node and peripheral blood of CLL patients is reshaped during venetoclax treatment. Blood advances. 3(17):2642-2652. https://doi.org/10.1182/bloodadvances.2019000360

MLA

Vancouver

Author

de Weerdt, Iris ; Hofland, Tom ; de Boer, Renate ; Dobber, Johan A ; Dubois, Julie ; van Nieuwenhuize, Denise ; Mobasher, Mehrdad ; de Boer, Fransien ; Hoogendoorn, Mels ; Velders, Gerjo A ; van der Klift, Marjolein ; Remmerswaal, Ester B M ; Bemelman, Frederike J ; Niemann, Carsten U ; Kersting, Sabina ; Levin, Mark-David ; Eldering, Eric ; Tonino, Sanne H ; Kater, Arnon P. / Distinct immune composition in lymph node and peripheral blood of CLL patients is reshaped during venetoclax treatment. I: Blood advances. 2019 ; Bind 3, Nr. 17. s. 2642-2652.

Bibtex

@article{3129759042a94a44b6a6661dbd4648b9,
title = "Distinct immune composition in lymph node and peripheral blood of CLL patients is reshaped during venetoclax treatment",
abstract = "Morbidity and mortality due to immunosuppression remain among the foremost clinical challenges in chronic lymphocytic leukemia (CLL). Although immunosuppression is considered to originate within the lymph node (LN) microenvironment, alterations in T and natural killer (NK) cells have almost exclusively been studied in peripheral blood (PB). Whereas chemoimmunotherapy further deteriorates immune function, novel targeted agents like the B-cell lymphoma 2 inhibitor venetoclax potentially spare nonmalignant lymphocytes; however, the effects of venetoclax on nonleukemic cells have not been explored. We address these unresolved issues using a comprehensive analysis of nonmalignant lymphocytes in paired LN and PB samples from untreated CLL patients, and by analyzing the effects of venetoclax-based treatment regimens on the immune system in PB samples from previously untreated and relapsed/refractory patients. CLL-derived LNs contained twice the amount of suppressive regulatory T cells (Tregs) and CLL supportive follicular T helper (Tfh) cells compared with PB. This was accompanied by a low frequency of cytotoxic lymphocytes. The expression of PD-1 by CD8+ T cells was significantly higher in LN compared with PB. Venetoclax-based treatment led to deep responses in the majority of patients, but also to decreased absolute numbers of B, T, and NK cells. Tfh cell, Treg, and PD-1+ CD8+ T cell numbers were reduced more than fivefold after venetoclax-based therapy, and overproduction of inflammatory cytokines was reduced. Furthermore, we observed restoration of NK cell function. These data support the notion that the immunosuppressive state in CLL is more prominent within the LN. Venetoclax-based regimens reduced the immunosuppressive footprint of CLL, suggesting immune recovery after the elimination of leukemic cells.",
author = "{de Weerdt}, Iris and Tom Hofland and {de Boer}, Renate and Dobber, {Johan A} and Julie Dubois and {van Nieuwenhuize}, Denise and Mehrdad Mobasher and {de Boer}, Fransien and Mels Hoogendoorn and Velders, {Gerjo A} and {van der Klift}, Marjolein and Remmerswaal, {Ester B M} and Bemelman, {Frederike J} and Niemann, {Carsten U} and Sabina Kersting and Mark-David Levin and Eric Eldering and Tonino, {Sanne H} and Kater, {Arnon P}",
note = "{\circledC} 2019 by The American Society of Hematology.",
year = "2019",
month = "9",
day = "10",
doi = "10.1182/bloodadvances.2019000360",
language = "English",
volume = "3",
pages = "2642--2652",
journal = "Blood advances",
issn = "2473-9529",
publisher = "American Society of Hematology",
number = "17",

}

RIS

TY - JOUR

T1 - Distinct immune composition in lymph node and peripheral blood of CLL patients is reshaped during venetoclax treatment

AU - de Weerdt, Iris

AU - Hofland, Tom

AU - de Boer, Renate

AU - Dobber, Johan A

AU - Dubois, Julie

AU - van Nieuwenhuize, Denise

AU - Mobasher, Mehrdad

AU - de Boer, Fransien

AU - Hoogendoorn, Mels

AU - Velders, Gerjo A

AU - van der Klift, Marjolein

AU - Remmerswaal, Ester B M

AU - Bemelman, Frederike J

AU - Niemann, Carsten U

AU - Kersting, Sabina

AU - Levin, Mark-David

AU - Eldering, Eric

AU - Tonino, Sanne H

AU - Kater, Arnon P

N1 - © 2019 by The American Society of Hematology.

PY - 2019/9/10

Y1 - 2019/9/10

N2 - Morbidity and mortality due to immunosuppression remain among the foremost clinical challenges in chronic lymphocytic leukemia (CLL). Although immunosuppression is considered to originate within the lymph node (LN) microenvironment, alterations in T and natural killer (NK) cells have almost exclusively been studied in peripheral blood (PB). Whereas chemoimmunotherapy further deteriorates immune function, novel targeted agents like the B-cell lymphoma 2 inhibitor venetoclax potentially spare nonmalignant lymphocytes; however, the effects of venetoclax on nonleukemic cells have not been explored. We address these unresolved issues using a comprehensive analysis of nonmalignant lymphocytes in paired LN and PB samples from untreated CLL patients, and by analyzing the effects of venetoclax-based treatment regimens on the immune system in PB samples from previously untreated and relapsed/refractory patients. CLL-derived LNs contained twice the amount of suppressive regulatory T cells (Tregs) and CLL supportive follicular T helper (Tfh) cells compared with PB. This was accompanied by a low frequency of cytotoxic lymphocytes. The expression of PD-1 by CD8+ T cells was significantly higher in LN compared with PB. Venetoclax-based treatment led to deep responses in the majority of patients, but also to decreased absolute numbers of B, T, and NK cells. Tfh cell, Treg, and PD-1+ CD8+ T cell numbers were reduced more than fivefold after venetoclax-based therapy, and overproduction of inflammatory cytokines was reduced. Furthermore, we observed restoration of NK cell function. These data support the notion that the immunosuppressive state in CLL is more prominent within the LN. Venetoclax-based regimens reduced the immunosuppressive footprint of CLL, suggesting immune recovery after the elimination of leukemic cells.

AB - Morbidity and mortality due to immunosuppression remain among the foremost clinical challenges in chronic lymphocytic leukemia (CLL). Although immunosuppression is considered to originate within the lymph node (LN) microenvironment, alterations in T and natural killer (NK) cells have almost exclusively been studied in peripheral blood (PB). Whereas chemoimmunotherapy further deteriorates immune function, novel targeted agents like the B-cell lymphoma 2 inhibitor venetoclax potentially spare nonmalignant lymphocytes; however, the effects of venetoclax on nonleukemic cells have not been explored. We address these unresolved issues using a comprehensive analysis of nonmalignant lymphocytes in paired LN and PB samples from untreated CLL patients, and by analyzing the effects of venetoclax-based treatment regimens on the immune system in PB samples from previously untreated and relapsed/refractory patients. CLL-derived LNs contained twice the amount of suppressive regulatory T cells (Tregs) and CLL supportive follicular T helper (Tfh) cells compared with PB. This was accompanied by a low frequency of cytotoxic lymphocytes. The expression of PD-1 by CD8+ T cells was significantly higher in LN compared with PB. Venetoclax-based treatment led to deep responses in the majority of patients, but also to decreased absolute numbers of B, T, and NK cells. Tfh cell, Treg, and PD-1+ CD8+ T cell numbers were reduced more than fivefold after venetoclax-based therapy, and overproduction of inflammatory cytokines was reduced. Furthermore, we observed restoration of NK cell function. These data support the notion that the immunosuppressive state in CLL is more prominent within the LN. Venetoclax-based regimens reduced the immunosuppressive footprint of CLL, suggesting immune recovery after the elimination of leukemic cells.

UR - http://www.scopus.com/inward/record.url?scp=85072284565&partnerID=8YFLogxK

U2 - 10.1182/bloodadvances.2019000360

DO - 10.1182/bloodadvances.2019000360

M3 - Journal article

VL - 3

SP - 2642

EP - 2652

JO - Blood advances

JF - Blood advances

SN - 2473-9529

IS - 17

ER -

ID: 58441968