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摘要 : 肿瘤发生会与炎性微环境密切相关,这个事实已经非常明确了。在一项新的研究中,荷兰癌症中心的Karin de Visser及同事对在一个乳腺癌小鼠模型中观察到的更多全身性炎症效应进行了分析评估。

 肿瘤发生会与炎性微环境密切相关,这个事实已经非常明确了。在一项新的研究中,荷兰癌症中心的Karin de Visser及同事对在一个乳腺癌小鼠模型中观察到的更多全身性炎症效应进行了分析评估。他们发现,肿瘤中白介素(IL)-1β 的表达会在局部层面上诱发γδ T细胞中IL-17的表达,后者通过 “粒细胞集落刺激因子”的生成促进嗜中性粒细胞在多个器官中的系统性积累。对这一事件级联的干预(比如说在嗜中性粒细胞激活的层面上进行干预),在这一乳腺癌模型中可以降低癌细胞向肺和淋巴结的转移。这些发现说明由局部肿瘤诱发的系统性(全身性)效应也许要比预测的更为广泛,同时也提供了多个潜在的治疗干预点。


IL-17-producing γδ T cells and neutrophils conspire to promote breast cancer metastasis


metastatic disease remains the primary cause of death for patients with breast cancer. The different steps of the metastatic cascade rely on reciprocal interactions between cancer cells and their microenvironment. Within this local microenvironment and in distant organs, immune cells and their mediators are known to facilitate metastasis formation1, 2. However, the precise contribution of tumour-induced systemic inflammation to metastasis and the mechanisms regulating systemic inflammation are poorly understood. Here we show that tumours maximize their chance of metastasizing by evoking a systemic inflammatory cascade in mouse models of spontaneous breast cancer metastasis. We mechanistically demonstrate that interleukin (IL)-1β elicits IL-17 expression from gamma delta (γδ) T cells, resulting in systemic, granulocyte colony-stimulating factor (G-CSF)-dependent expansion and polarization of neutrophils in mice bearing mammary tumours. Tumour-induced neutrophils acquire the ability to suppress cytotoxic T lymphocytes carrying the CD8 antigen, which limit the establishment of metastases. Neutralization of IL-17 or G-CSF and absence of γδ T cells prevents neutrophil accumulation and downregulates the T-cell-suppressive phenotype of neutrophils. Moreover, the absence of γδ T cells or neutrophils profoundly reduces pulmonary and lymph node metastases without influencing primary tumour progression. Our data indicate that targeting this novel cancer-cell-initiated domino effect within the immune system—the γδ T cell/IL-17/neutrophil axis—represents a new strategy to inhibit metastatic disease.

来源: Nature 浏览次数:0


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