Jiang Zhujun, Chen Jingtao, Du Xuemei, Cheng Hang, Wang Xiaohu, Dong Chen
Institute for Immunology and School of Medicine, Tsinghua University, Beijing, 100084, China.
Institute of Translational Medicine, The First Hospital, Jilin University, Changchun, 130031, China.
Protein Cell. 2017 Mar;8(3):191-201. doi: 10.1007/s13238-016-0345-7. Epub 2016 Dec 1.
Metastasis is the leading cause of death in breast cancer patients. However, the mechanisms underlying metastasis are not well understood and there is no effective treatment in the clinic. Here, we demonstrate that in MMTV-PyMT, a highly malignant spontaneous breast tumor model, IL-25 (also called IL-17E) was expressed by tumor-infiltrating CD4 T cells and macrophages. An IL-25 neutralization antibody, while not affecting primary tumor growth, substantially reduced lung metastasis. Inhibition of IL-25 resulted in decreased type 2 T cells and macrophages in the primary tumor microenvironments, both reported to enhance breast tumor invasion and subsequent metastasis to the lung. Taken together, our data suggest IL-25 blockade as a novel treatment for metastatic breast tumor.
转移是乳腺癌患者死亡的主要原因。然而，转移的潜在机制尚未完全明确，临床上也没有有效的治疗方法。在此，我们证明，在MMTV-PyMT（一种高度恶性的自发性乳腺肿瘤模型）中，肿瘤浸润性CD4 T细胞和巨噬细胞表达白细胞介素-25（也称为IL-17E）。一种白细胞介素-25中和抗体，在不影响原发性肿瘤生长的情况下，能显著减少肺转移。抑制白细胞介素-25会导致原发性肿瘤微环境中2型T细胞和巨噬细胞数量减少，这两种细胞均被报道可增强乳腺肿瘤的侵袭及随后的肺转移。综上所述，我们的数据表明，阻断白细胞介素-25可作为转移性乳腺肿瘤的一种新的治疗方法。
