Dendritic cells (DCs) are well known for their capacity to induce adaptive antitumor immune response through Ag presentation and tumor-specific T cell activation. Recent findings reveal that besides this role, DCs may display additional antitumor effects. In this study, we provide evidence that LPS- or IFN-gamma-activated rat bone marrow-derived dendritic cells (BMDCs) display killing properties against tumor cells. These cytotoxic BMDCs exhibit a mature DC phenotype, produce high amounts of IL-12, IL-6, and TNF-alpha, and retain their phagocytic properties. BMDC-mediated tumor cell killing requires cell-cell contact and depends on NO production, but not on perforin/granzyme or on death receptors. Furthermore, dead tumor cells do not exhibit characteristics of apoptosis. Thus, intratumoral LPS injections induce an increase of inducible NO synthase expression in tumor-infiltrating DCs associated with a significant arrest of tumor growth. Altogether, these results suggest that LPS-activated BMDCs represent powerful tumoricidal cells which enforce their potential as anticancer cellular vaccines.

译文

树突状细胞(DCs)以通过Ag呈递和肿瘤特异性T细胞活化而诱导适应性抗肿瘤免疫反应的能力而闻名。最近的发现表明,除这种作用外,DC可能还显示出额外的抗肿瘤作用。在这项研究中,我们提供的证据表明LPS或IFN-γ激活的大鼠骨髓源性树突状细胞(BMDC)表现出对肿瘤细胞的杀伤特性。这些细胞毒性BMDC表现出成熟的DC表型,产生大量的IL-12,IL-6和TNF-α,并保留其吞噬特性。 BMDC介导的肿瘤细胞杀伤需要细胞与细胞的接触,并取决于NO的产生,而不取决于穿孔素/粒酶或死亡受体。此外,死亡的肿瘤细胞不表现出凋亡特征。因此,肿瘤内LPS注射诱导与肿瘤生长的显着停滞相关的肿瘤浸润DC中诱导型NO合酶表达的增加。总而言之,这些结果表明,LPS激活的BMDC代表了强大的杀伤性细胞,可增强其作为抗癌细胞疫苗的潜力。

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