Milk fat globule epidermal growth factor-8 blockade triggers tumor destruction through coordinated cell-autonomous and immune-mediated mechanisms.
Milk fat globule epidermal growth factor-8 blockade triggers tumor destruction through coordinated cell-autonomous and immune-mediated mechanisms.
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DOI：
10.1084/jem.20082614
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发表时间：
2009-06-08
期刊：
影响因子：
--
通讯作者：
Tahara H
中科院分区：
文献类型：
--
作者：
Jinushi M;Sato M;Kanamoto A;Itoh A;Nagai S;Koyasu S;Dranoff G;Tahara H
癌变反映了转化细胞和正常宿主元素的动态相互作用，但癌症治疗通常分别针对每个隔室。在肿瘤微环境中，分泌的蛋白质乳脂肪球表皮生长因子-8（MFG-E8）通过肿瘤和宿主细胞中协调的αvβ3整联蛋白信号传导刺激疾病进展。MFG-E8增强肿瘤细胞存活、侵袭和血管生成，并有助于局部免疫抑制。我们表明，系统性MFG-E8阻断与细胞毒性化疗，分子靶向治疗和放射治疗合作，以诱导破坏各种类型的已建立的小鼠肿瘤。联合治疗引起广泛的肿瘤细胞凋亡，其与死亡肿瘤细胞的有效树突细胞交叉呈递偶联。这种连接产生有效的抗肿瘤效应T细胞，但抑制FoxP 3 + T reg细胞，从而实现长期的保护性免疫。总的来说，这些发现表明，全身性MFG-E8阻断可能通过协调细胞自主和免疫介导的机制加强现有治疗方案的抗肿瘤活性。
Carcinogenesis reflects the dynamic interplay of transformed cells and normal host elements, but cancer treatments typically target each compartment separately. Within the tumor microenvironment, the secreted protein milk fat globule epidermal growth factor–8 (MFG-E8) stimulates disease progression through coordinated αvβ3 integrin signaling in tumor and host cells. MFG-E8 enhances tumor cell survival, invasion, and angiogenesis, and contributes to local immune suppression. We show that systemic MFG-E8 blockade cooperates with cytotoxic chemotherapy, molecularly targeted therapy, and radiation therapy to induce destruction of various types of established mouse tumors. The combination treatments evoke extensive tumor cell apoptosis that is coupled to efficient dendritic cell cross-presentation of dying tumor cells. This linkage engenders potent antitumor effector T cells but inhibits FoxP3+ T reg cells, thereby achieving long-term protective immunity. Collectively, these findings suggest that systemic MFG-E8 blockade might intensify the antitumor activities of existing therapeutic regimens through coordinated cell-autonomous and immune-mediated mechanisms.
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影响因子：
11.2
作者：
Jinushi, Masahisa;Nakazaki, Yukoh;Dranoff, Glenn
通讯作者：
Dranoff, Glenn
影响因子：
15.9
作者：
Jinushi, Masahisa;Nakazaki, Yukoh;Dranoff, Glenn
通讯作者：
Dranoff, Glenn
影响因子：
45.3
作者：
Druker, BJ
通讯作者：
Druker, BJ
DOI：
10.1073/pnas.0707421104
发表时间：
2007-10-02
影响因子：
11.1
作者：
Lacy-Hulbert, Adam;Smith, Aileen M.;Hynes, Richard O.
通讯作者：
Hynes, Richard O.
DOI：
10.1084/jem.20071019
发表时间：
2008-06-09
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kranich J;Krautler NJ;Heinen E;Polymenidou M;Bridel C;Schildknecht A;Huber C;Kosco-Vilbois MH;Zinkernagel R;Miele G;Aguzzi A
通讯作者：
Aguzzi A