Inactivation of PI(3)K p110δ breaks regulatory T-cell-mediated immune tolerance to cancer.
Inactivation of PI(3)K p110δ breaks regulatory T-cell-mediated immune tolerance to cancer.
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DOI：
10.1038/nature13444
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发表时间：
2014-06-19
期刊：
影响因子：
64.8
通讯作者：
Vanhaesebroeck B
中科院分区：
文献类型：
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作者：
Ali K;Soond DR;Pineiro R;Hagemann T;Pearce W;Lim EL;Bouabe H;Scudamore CL;Hancox T;Maecker H;Friedman L;Turner M;Okkenhaug K;Vanhaesebroeck B
PI3K p110δ 亚型抑制剂在某些人类白血病中显示出显着的治疗效果。由于p110δ主要在白细胞中表达，因此针对p110δ的药物尚未被考虑用于治疗实体瘤。我们在此报告，小鼠体内 p110δ 失活可预防多种癌症，包括非血液实体瘤。我们证明调节性 T 细胞 (Treg) 中的 p110δ 失活会释放 CD8+ 细胞毒性 T 细胞并诱导肿瘤消退。因此，p110δ抑制剂可以破坏肿瘤诱导的免疫耐受，应考虑在肿瘤学中更广泛地使用。
Inhibitors against the p110δ isoform of PI3K have shown remarkable therapeutic efficacy in some human leukaemias. Since p110δ is primarily expressed in leukocytes, drugs against p110δ have not been considered for the treatment of solid tumours. We report here that p110δ inactivation in mice protects against a broad range of cancers, including non-haematological solid tumours. We demonstrate that p110δ inactivation in regulatory T cells (Treg) unleashes CD8+ cytotoxic T cells and induces tumour regression. Thus, p110δ inhibitors can break tumour-induced immune tolerance and should be considered for wider use in oncology.