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Ibrutinib treatment inhibits breast cancer progression and metastasis by inducing conversion of myeloid-derived suppressor cells to dendritic cells

BACKGROUND: Ibrutinib is a Bruton’s tyrosine kinase (BTK) and interleukin-2-inducible kinase (ITK) inhibitor used for treating chronic lymphocytic leukaemia (CLL) and other cancers. Although ibrutinib is known to inhibit the growth of breast cancer cell growth in vitro, its impact on the treatment a...

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Autores principales: Varikuti, Sanjay, Singh, Bhawana, Volpedo, Greta, Ahirwar, Dinesh K., Jha, Bijay K., Saljoughian, Noushin, Viana, Agostinho G., Verma, Chaitenya, Hamza, Omar, Halsey, Gregory, Holcomb, Erin A., Maryala, Ritvik J., Oghumu, Steve, Ganju, Ramesh K., Satoskar, Abhay R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7109110/
https://www.ncbi.nlm.nih.gov/pubmed/32025027
http://dx.doi.org/10.1038/s41416-020-0743-8
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author Varikuti, Sanjay
Singh, Bhawana
Volpedo, Greta
Ahirwar, Dinesh K.
Jha, Bijay K.
Saljoughian, Noushin
Viana, Agostinho G.
Verma, Chaitenya
Hamza, Omar
Halsey, Gregory
Holcomb, Erin A.
Maryala, Ritvik J.
Oghumu, Steve
Ganju, Ramesh K.
Satoskar, Abhay R.
author_facet Varikuti, Sanjay
Singh, Bhawana
Volpedo, Greta
Ahirwar, Dinesh K.
Jha, Bijay K.
Saljoughian, Noushin
Viana, Agostinho G.
Verma, Chaitenya
Hamza, Omar
Halsey, Gregory
Holcomb, Erin A.
Maryala, Ritvik J.
Oghumu, Steve
Ganju, Ramesh K.
Satoskar, Abhay R.
author_sort Varikuti, Sanjay
collection PubMed
description BACKGROUND: Ibrutinib is a Bruton’s tyrosine kinase (BTK) and interleukin-2-inducible kinase (ITK) inhibitor used for treating chronic lymphocytic leukaemia (CLL) and other cancers. Although ibrutinib is known to inhibit the growth of breast cancer cell growth in vitro, its impact on the treatment and metastasis of breast cancer is unclear. METHODS: Using an orthotopic mouse breast cancer model, we show that ibrutinib inhibits the progression and metastasis of breast cancer. RESULTS: Ibrutinib inhibited proliferation of cancer cells in vitro, and Ibrutinib-treated mice displayed significantly lower tumour burdens and metastasis compared to controls. Furthermore, the spleens and tumours from Ibrutinib-treated mice contained more mature DCs and lower numbers of myeloid-derived suppressor cells (MDSCs), which promote disease progression and are linked to poor prognosis. We also confirmed that ex vivo treatment of MDSCs with ibrutinib switched their phenotype to mature DCs and significantly enhanced MHCII expression. Further, ibrutinib treatment promoted T cell proliferation and effector functions leading to the induction of antitumour T(H)1 and CTL immune responses. CONCLUSIONS: Ibrutinib inhibits tumour development and metastasis in breast cancer by promoting the development of mature DCs from MDSCs and hence could be a novel therapeutic agent for the treatment of breast cancer.
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spelling pubmed-71091102021-02-06 Ibrutinib treatment inhibits breast cancer progression and metastasis by inducing conversion of myeloid-derived suppressor cells to dendritic cells Varikuti, Sanjay Singh, Bhawana Volpedo, Greta Ahirwar, Dinesh K. Jha, Bijay K. Saljoughian, Noushin Viana, Agostinho G. Verma, Chaitenya Hamza, Omar Halsey, Gregory Holcomb, Erin A. Maryala, Ritvik J. Oghumu, Steve Ganju, Ramesh K. Satoskar, Abhay R. Br J Cancer Article BACKGROUND: Ibrutinib is a Bruton’s tyrosine kinase (BTK) and interleukin-2-inducible kinase (ITK) inhibitor used for treating chronic lymphocytic leukaemia (CLL) and other cancers. Although ibrutinib is known to inhibit the growth of breast cancer cell growth in vitro, its impact on the treatment and metastasis of breast cancer is unclear. METHODS: Using an orthotopic mouse breast cancer model, we show that ibrutinib inhibits the progression and metastasis of breast cancer. RESULTS: Ibrutinib inhibited proliferation of cancer cells in vitro, and Ibrutinib-treated mice displayed significantly lower tumour burdens and metastasis compared to controls. Furthermore, the spleens and tumours from Ibrutinib-treated mice contained more mature DCs and lower numbers of myeloid-derived suppressor cells (MDSCs), which promote disease progression and are linked to poor prognosis. We also confirmed that ex vivo treatment of MDSCs with ibrutinib switched their phenotype to mature DCs and significantly enhanced MHCII expression. Further, ibrutinib treatment promoted T cell proliferation and effector functions leading to the induction of antitumour T(H)1 and CTL immune responses. CONCLUSIONS: Ibrutinib inhibits tumour development and metastasis in breast cancer by promoting the development of mature DCs from MDSCs and hence could be a novel therapeutic agent for the treatment of breast cancer. Nature Publishing Group UK 2020-02-06 2020-03-31 /pmc/articles/PMC7109110/ /pubmed/32025027 http://dx.doi.org/10.1038/s41416-020-0743-8 Text en © The Author(s), under exclusive licence to Cancer Research UK 2020 https://creativecommons.org/licenses/by/4.0/Note This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0).
spellingShingle Article
Varikuti, Sanjay
Singh, Bhawana
Volpedo, Greta
Ahirwar, Dinesh K.
Jha, Bijay K.
Saljoughian, Noushin
Viana, Agostinho G.
Verma, Chaitenya
Hamza, Omar
Halsey, Gregory
Holcomb, Erin A.
Maryala, Ritvik J.
Oghumu, Steve
Ganju, Ramesh K.
Satoskar, Abhay R.
Ibrutinib treatment inhibits breast cancer progression and metastasis by inducing conversion of myeloid-derived suppressor cells to dendritic cells
title Ibrutinib treatment inhibits breast cancer progression and metastasis by inducing conversion of myeloid-derived suppressor cells to dendritic cells
title_full Ibrutinib treatment inhibits breast cancer progression and metastasis by inducing conversion of myeloid-derived suppressor cells to dendritic cells
title_fullStr Ibrutinib treatment inhibits breast cancer progression and metastasis by inducing conversion of myeloid-derived suppressor cells to dendritic cells
title_full_unstemmed Ibrutinib treatment inhibits breast cancer progression and metastasis by inducing conversion of myeloid-derived suppressor cells to dendritic cells
title_short Ibrutinib treatment inhibits breast cancer progression and metastasis by inducing conversion of myeloid-derived suppressor cells to dendritic cells
title_sort ibrutinib treatment inhibits breast cancer progression and metastasis by inducing conversion of myeloid-derived suppressor cells to dendritic cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7109110/
https://www.ncbi.nlm.nih.gov/pubmed/32025027
http://dx.doi.org/10.1038/s41416-020-0743-8
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