Department of Pathology, The Ohio State University Medical Center, Columbus, OH, USA.
Department of Microbiology, The Ohio State University, Columbus, OH, USA.
Br J Cancer. 2020 Mar;122(7):1005-1013. doi: 10.1038/s41416-020-0743-8. Epub 2020 Feb 6.
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.
Using an orthotopic mouse breast cancer model, we show that ibrutinib inhibits the progression and metastasis of breast cancer.
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 T1 and CTL immune responses.
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.
伊布替尼是一种布鲁顿酪氨酸激酶（BTK）和白细胞介素-2 可诱导激酶（ITK）抑制剂，用于治疗慢性淋巴细胞白血病（CLL）和其他癌症。虽然已知伊布替尼可抑制体外乳腺癌细胞的生长，但它对乳腺癌的治疗和转移的影响尚不清楚。
我们使用原位乳腺癌小鼠模型表明，伊布替尼可抑制乳腺癌的进展和转移。
伊布替尼可抑制癌细胞在体外的增殖，与对照组相比，伊布替尼治疗的小鼠肿瘤负荷和转移明显降低。此外，伊布替尼治疗的小鼠的脾脏和肿瘤中含有更多成熟的树突状细胞（DC）和较少的髓系来源的抑制细胞（MDSC），这些细胞促进疾病进展并与不良预后相关。我们还证实，伊布替尼对 MDSC 的体外治疗将其表型转变为成熟的 DC，并显著增强 MHCII 的表达。此外，伊布替尼治疗可促进 T 细胞增殖和效应功能，从而诱导抗肿瘤 T1 和 CTL 免疫反应。
伊布替尼通过促进 MDSC 向成熟 DC 的发育来抑制乳腺癌中的肿瘤发展和转移，因此可能成为治疗乳腺癌的一种新的治疗剂。
