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.
Abstract
Abstract
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 TH1 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.
Publisher
Springer Science and Business Media LLC
Cited by
56 articles.
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