研究人員在日前在線出版的《自然—免疫學》期刊上報告,,免疫感應器的活性和腫瘤逃逸免疫系統(tǒng)的能力間存在一種看似不合邏輯的聯(lián)系,。這個意料之外的結果揭示了癌癥治療的一個新靶標。
這個輔助系統(tǒng)是由一串級聯(lián)狀的蛋白質組成,,當感染出現時,,它會像火警系統(tǒng)一樣向免疫系統(tǒng)發(fā)出警告。一個奇怪的曲折中,,Lambris和同事發(fā)現腫瘤激活了一種補充蛋白質C5,,這樣,在事實上抑制了免疫系統(tǒng)的抗腫瘤反應,。
這是一個令人驚異的結果,,作者通過觀察發(fā)現,被激活的蛋白質征召“抑制”細胞到相應位點,。這些行動解除了其他免疫細胞的功能,,阻止它們殺死腫瘤。重要的是,,他們的研究顯示,,阻止C5的活性能降低小鼠腫瘤的生長,其效果相當于抗腫瘤藥物泰素(taxol)的治療效果,。(生物谷Bioon.com)
生物谷推薦原始出處:
Nature Immunology,,9, 1225 - 1235,Maciej M Markiewski,,John D Lambris
Modulation of the antitumor immune response by complement
Maciej M Markiewski1, Robert A DeAngelis1, Fabian Benencia2,4, Salome K Ricklin-Lichtsteiner1, Anna Koutoulaki1, Craig Gerard3, George Coukos2 & John D Lambris1
The involvement of complement-activation products in promoting tumor growth has not yet been recognized. Here we show that the generation of complement C5a in a tumor microenvironment enhanced tumor growth by suppressing the antitumor CD8+ T cell–mediated response. This suppression was associated with the recruitment of myeloid-derived suppressor cells into tumors and augmentation of their T cell–directed suppressive abilities. Amplification of the suppressive capacity of myeloid-derived suppressor cells by C5a occurred through regulation of the production of reactive oxygen and nitrogen species. Pharmacological blockade of the C5a receptor considerably impaired tumor growth to a degree similar to the effect produced by the anticancer drug paclitaxel. Thus, our study demonstrates a therapeutic function for complement inhibition in the treatment of cancer.
1 Department of Pathology and Laboratory Medicine, Medical School of the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
2 Center for Research on Reproduction and Women's Health, Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
3 Pulmonary Division, Children's Hospital, Boston, Massachusetts 02215, USA.
4 Present address: Department of Biomedical Sciences, College of Osteopathic Medicine and Biomedical Engineering Program, Russ College of Engineering and Technology, University of Ohio, Athens, Ohio 45701, USA.