Shurin Galina V, Tourkova Irina L, Shurin Michael R
Department of Pathology, Division of Clinical Immunopathology, University of Pittsburgh Medical Center, Pittsburgh, PA 15261, USA.
J Immunother. 2008 Jun;31(5):491-9. doi: 10.1097/CJI.0b013e318176fae4.
Conventional chemotherapy targets dividing tumor cells and might support antitumor immunity by providing tumor antigens from dying tumor cells to antigen-presenting dendritic cells (DCs). Despite emerging evidence to suggest that phagocytosis of dying tumor cells by DCs requires membrane targeting of specific small Rho guanosine triphosphatases (GTPases), nothing is known with regard to the direct effect of chemotherapeutic agents on low molecular weight Rho GTPases in DCs. Prompted by a recent observation that low-dose chemotherapeutic drug paclitaxel could up-regulate DC maturation and function, here we studied putative regulatory roles for various chemotherapeutic agents in modulating small Rho GTPases in DC. Our results demonstrate that different classes of chemotherapeutic drugs at low nontoxic concentrations regulate activity of Rac, RhoA, and RhoE in murine DC, suggesting that small Rho GTPases might serve as new targets for modulating functional activity of DC vaccines or endogenous DCs in various immunotherapeutic or chemoimmunotherapeutic strategies.
传统化疗靶向分裂的肿瘤细胞，并可能通过将垂死肿瘤细胞中的肿瘤抗原提供给抗原呈递树突状细胞（DC）来支持抗肿瘤免疫。尽管有新证据表明DC对垂死肿瘤细胞的吞噬作用需要特定的小分子Rho鸟苷三磷酸酶（GTP酶）进行膜靶向，但关于化疗药物对DC中低分子量Rho GTP酶的直接作用尚不清楚。最近观察到低剂量化疗药物紫杉醇可上调DC的成熟和功能，在此基础上，我们研究了各种化疗药物在调节DC中微小Rho GTP酶方面的假定调节作用。我们的结果表明，低无毒浓度的不同类别化疗药物可调节小鼠DC中Rac、RhoA和RhoE的活性，这表明微小Rho GTP酶可能成为在各种免疫治疗或化学免疫治疗策略中调节DC疫苗或内源性DC功能活性的新靶点。
