颗粒酶B的表达在人单核细胞中被Toll样受体8（TLR8）激动剂增强，并有助于抗体依赖性细胞毒性作用。
Granzyme B expression is enhanced in human monocytes by TLR8 agonists and contributes to antibody-dependent cellular cytotoxicity.
作者信息
Elavazhagan Saranya, Fatehchand Kavin, Santhanam Vikram, Fang Huiqing, Ren Li, Gautam Shalini, Reader Brenda, Mo Xiaokui, Cheney Carolyn, Briercheck Edward, Vasilakos John P, Dietsch Gregory N, Hershberg Robert M, Caligiuri Michael, Byrd John C, Butchar Jonathan P, Tridandapani Susheela
机构信息
Department of Internal Medicine, The Ohio State University, Columbus, OH 43210;
Center for Biostatistics, The Ohio State University, Columbus, OH 43210;
出版信息
J Immunol. 2015 Mar 15;194(6):2786-95. doi: 10.4049/jimmunol.1402316. Epub 2015 Feb 9.
FcγRs are critical mediators of mAb cancer therapies, because they drive cytotoxic processes upon binding of effector cells to opsonized targets. Along with NK cells, monocytes are also known to destroy Ab-coated targets via Ab-dependent cellular cytotoxicity (ADCC). However, the precise mechanisms by which monocytes carry out this function have remained elusive. In this article, we show that human monocytes produce the protease granzyme B upon both FcγR and TLR8 activation. Treatment with TLR8 agonists elicited granzyme B and also enhanced FcγR-mediated granzyme B production in an additive fashion. Furthermore, monocyte-mediated ADCC against cetuximab-coated tumor targets was enhanced by TLR8 agonist treatment, and this enhancement of ADCC required granzyme B. Hence we have identified granzyme B as an important mediator of FcγR function in human monocytes and have uncovered another mechanism by which TLR8 agonists may enhance FcγR-based therapies.
FcγR是单克隆抗体癌症治疗的关键介质，因为它们在效应细胞与调理素化的靶标结合时驱动细胞毒性过程。与自然杀伤细胞一样，单核细胞也已知通过抗体依赖性细胞毒性（ADCC）破坏抗体包被的靶标。然而，单核细胞执行此功能的确切机制仍然难以捉摸。在本文中，我们表明人类单核细胞在FcγR和TLR8激活时都会产生蛋白酶颗粒酶B。用TLR8激动剂处理可诱导颗粒酶B产生，并且还以累加方式增强FcγR介导的颗粒酶B产生。此外，TLR8激动剂处理增强了单核细胞介导的针对西妥昔单抗包被的肿瘤靶标的ADCC，而这种ADCC的增强需要颗粒酶B。因此，我们已确定颗粒酶B是人类单核细胞中FcγR功能的重要介质，并揭示了TLR8激动剂可能增强基于FcγR的治疗的另一种机制。
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