Modulation of the antitumor immune response by complement.
Modulation of the antitumor immune response by complement.
复制标题
作者：
补体激活产物参与促进肿瘤生长尚未被认识到。在这里，我们表明，在肿瘤微环境中产生的补体C5a通过抑制抗肿瘤CD8+ T细胞介导的反应来增强肿瘤生长。这种抑制与髓源性抑制细胞（MDSC）进入肿瘤的募集和增强其T细胞定向抑制能力有关。C5a通过调节活性氧和氮的产生来放大MDSC的抑制能力。C5a受体的药理学阻断显著损害肿瘤生长，其程度与抗癌药物紫杉醇产生的效果相当。因此，本研究证明了补体抑制在癌症治疗中的治疗作用。
The involvement of complement activation products in promoting tumor growth has not yet been recognized. Here we show that generation of complement C5a in the tumor microenvironment enhanced tumor growth by suppressing the anti-tumor CD8+ T cell-mediated response. This suppression was associated with the recruitment of myeloid-derived suppressor cells (MDSCs) into tumors and augmentation of their T cell-directed suppressive capabilities. Amplification of MDSC suppressive capacity by C5a occurred through regulation of the production of reactive oxygen and nitrogen species. Pharmacological blockade of C5a receptor significantly impaired tumor growth to a degree comparable to the effect produced by the anti-cancer drug Taxol. Thus, this study demonstrates a therapeutic role for complement inhibition in the treatment of cancer.