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Targeting arginase-1 exerts antitumor effects in multiple myeloma and mitigates bortezomib-induced cardiotoxicity

Multiple myeloma (MM) remains an incurable malignancy of plasma cells despite constantly evolving therapeutic approaches including various types of immunotherapy. Increased arginase activity has been associated with potent suppression of T-cell immune responses in different types of cancer. Here, we...

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Autores principales: Ramji, Kavita, Grzywa, Tomasz M., Sosnowska, Anna, Paterek, Aleksandra, Okninska, Marta, Pilch, Zofia, Barankiewicz, Joanna, Garbicz, Filip, Borg, Katarzyna, Bany-Laszewicz, Urszula, Zerrouqi, Abdesamad, Pyrzynska, Beata, Rodziewicz-Lurzynska, Anna, Papiernik, Diana, Sklepkiewicz, Piotr, Kedzierska, Hanna, Staruch, Adam, Sadowski, Radoslaw, Ciepiela, Olga, Lech-Maranda, Ewa, Juszczynski, Przemyslaw, Mackiewicz, Urszula, Maczewski, Michal, Nowis, Dominika, Golab, Jakub
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9668840/
https://www.ncbi.nlm.nih.gov/pubmed/36385153
http://dx.doi.org/10.1038/s41598-022-24137-1
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author Ramji, Kavita
Grzywa, Tomasz M.
Sosnowska, Anna
Paterek, Aleksandra
Okninska, Marta
Pilch, Zofia
Barankiewicz, Joanna
Garbicz, Filip
Borg, Katarzyna
Bany-Laszewicz, Urszula
Zerrouqi, Abdesamad
Pyrzynska, Beata
Rodziewicz-Lurzynska, Anna
Papiernik, Diana
Sklepkiewicz, Piotr
Kedzierska, Hanna
Staruch, Adam
Sadowski, Radoslaw
Ciepiela, Olga
Lech-Maranda, Ewa
Juszczynski, Przemyslaw
Mackiewicz, Urszula
Maczewski, Michal
Nowis, Dominika
Golab, Jakub
author_facet Ramji, Kavita
Grzywa, Tomasz M.
Sosnowska, Anna
Paterek, Aleksandra
Okninska, Marta
Pilch, Zofia
Barankiewicz, Joanna
Garbicz, Filip
Borg, Katarzyna
Bany-Laszewicz, Urszula
Zerrouqi, Abdesamad
Pyrzynska, Beata
Rodziewicz-Lurzynska, Anna
Papiernik, Diana
Sklepkiewicz, Piotr
Kedzierska, Hanna
Staruch, Adam
Sadowski, Radoslaw
Ciepiela, Olga
Lech-Maranda, Ewa
Juszczynski, Przemyslaw
Mackiewicz, Urszula
Maczewski, Michal
Nowis, Dominika
Golab, Jakub
author_sort Ramji, Kavita
collection PubMed
description Multiple myeloma (MM) remains an incurable malignancy of plasma cells despite constantly evolving therapeutic approaches including various types of immunotherapy. Increased arginase activity has been associated with potent suppression of T-cell immune responses in different types of cancer. Here, we investigated the role of arginase 1 (ARG1) in Vκ*MYC model of MM in mice. ARG1 expression in myeloid cells correlated with tumor progression and was accompanied by a systemic drop in ʟ-arginine levels. In MM-bearing mice antigen-induced proliferation of adoptively transferred T-cells was strongly suppressed and T-cell proliferation was restored by pharmacological arginase inhibition. Progression of Vκ*MYC tumors was significantly delayed in mice with myeloid-specific ARG1 deletion. Arginase inhibition effectively inhibited tumor progression although it failed to augment anti-myeloma effects of bortezomib. However, arginase inhibitor completely prevented development of bortezomib-induced cardiotoxicity in mice. Altogether, these findings indicate that arginase inhibitors could be further tested as a complementary strategy in multiple myeloma to mitigate adverse cardiac events without compromising antitumor efficacy of proteasome inhibitors.
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spelling pubmed-96688402022-11-18 Targeting arginase-1 exerts antitumor effects in multiple myeloma and mitigates bortezomib-induced cardiotoxicity Ramji, Kavita Grzywa, Tomasz M. Sosnowska, Anna Paterek, Aleksandra Okninska, Marta Pilch, Zofia Barankiewicz, Joanna Garbicz, Filip Borg, Katarzyna Bany-Laszewicz, Urszula Zerrouqi, Abdesamad Pyrzynska, Beata Rodziewicz-Lurzynska, Anna Papiernik, Diana Sklepkiewicz, Piotr Kedzierska, Hanna Staruch, Adam Sadowski, Radoslaw Ciepiela, Olga Lech-Maranda, Ewa Juszczynski, Przemyslaw Mackiewicz, Urszula Maczewski, Michal Nowis, Dominika Golab, Jakub Sci Rep Article Multiple myeloma (MM) remains an incurable malignancy of plasma cells despite constantly evolving therapeutic approaches including various types of immunotherapy. Increased arginase activity has been associated with potent suppression of T-cell immune responses in different types of cancer. Here, we investigated the role of arginase 1 (ARG1) in Vκ*MYC model of MM in mice. ARG1 expression in myeloid cells correlated with tumor progression and was accompanied by a systemic drop in ʟ-arginine levels. In MM-bearing mice antigen-induced proliferation of adoptively transferred T-cells was strongly suppressed and T-cell proliferation was restored by pharmacological arginase inhibition. Progression of Vκ*MYC tumors was significantly delayed in mice with myeloid-specific ARG1 deletion. Arginase inhibition effectively inhibited tumor progression although it failed to augment anti-myeloma effects of bortezomib. However, arginase inhibitor completely prevented development of bortezomib-induced cardiotoxicity in mice. Altogether, these findings indicate that arginase inhibitors could be further tested as a complementary strategy in multiple myeloma to mitigate adverse cardiac events without compromising antitumor efficacy of proteasome inhibitors. Nature Publishing Group UK 2022-11-16 /pmc/articles/PMC9668840/ /pubmed/36385153 http://dx.doi.org/10.1038/s41598-022-24137-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Ramji, Kavita
Grzywa, Tomasz M.
Sosnowska, Anna
Paterek, Aleksandra
Okninska, Marta
Pilch, Zofia
Barankiewicz, Joanna
Garbicz, Filip
Borg, Katarzyna
Bany-Laszewicz, Urszula
Zerrouqi, Abdesamad
Pyrzynska, Beata
Rodziewicz-Lurzynska, Anna
Papiernik, Diana
Sklepkiewicz, Piotr
Kedzierska, Hanna
Staruch, Adam
Sadowski, Radoslaw
Ciepiela, Olga
Lech-Maranda, Ewa
Juszczynski, Przemyslaw
Mackiewicz, Urszula
Maczewski, Michal
Nowis, Dominika
Golab, Jakub
Targeting arginase-1 exerts antitumor effects in multiple myeloma and mitigates bortezomib-induced cardiotoxicity
title Targeting arginase-1 exerts antitumor effects in multiple myeloma and mitigates bortezomib-induced cardiotoxicity
title_full Targeting arginase-1 exerts antitumor effects in multiple myeloma and mitigates bortezomib-induced cardiotoxicity
title_fullStr Targeting arginase-1 exerts antitumor effects in multiple myeloma and mitigates bortezomib-induced cardiotoxicity
title_full_unstemmed Targeting arginase-1 exerts antitumor effects in multiple myeloma and mitigates bortezomib-induced cardiotoxicity
title_short Targeting arginase-1 exerts antitumor effects in multiple myeloma and mitigates bortezomib-induced cardiotoxicity
title_sort targeting arginase-1 exerts antitumor effects in multiple myeloma and mitigates bortezomib-induced cardiotoxicity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9668840/
https://www.ncbi.nlm.nih.gov/pubmed/36385153
http://dx.doi.org/10.1038/s41598-022-24137-1
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