Department of Oncology, Sidney Kimmel Cancer Center, Division of Immunology, Johns Hopkins University, USA.
Cell Immunol. 2010;263(1):79-87. doi: 10.1016/j.cellimm.2010.03.001. Epub 2010 Mar 6.
Subclinical doses of Paclitaxel (PTX) given 1day prior to a HER-2/neu (neu)-targeted, granulocyte-macrophage colony stimulating factor (GM-CSF)-secreting whole-cell vaccine enhances neu-specific T cell responses and slows neu(+) tumor growth in tolerized HER-2/neu (neu-N) mice. We demonstrate that co-administration of PTX and Cyclophosphamide (CY) synergizes to slow tumor growth, and that in vitro, DC precursors exposed to PTX before LPS maturation results in greater co-stimulatory molecule expression, IL-12 production, and the ability to induce CD8(+) T cells with enhanced lytic activity against neu(+) tumors. PTX treatment also enhances maturation marker expression on CD11c(+) DCs isolated from vaccine-draining lymph nodes. Ex vivo, these DCs activate CD8(+) T cells with greater lytic capability than DC's from vaccine alone-treated neu-N mice. Finally, PTX treatment results in enhanced antigen-specific, IFN-gamma-secreting CD8(+) T cells in vivo. Thus, administration of PTX with a tumor vaccine improves T cell priming through enhanced maturation of DC.
亚临床剂量的紫杉醇（PTX）在给予 HER-2/neu（neu）靶向、粒细胞-巨噬细胞集落刺激因子（GM-CSF）分泌的全细胞疫苗前 1 天给药，可增强 neu 特异性 T 细胞反应，并在耐受 HER-2/neu（neu-N）小鼠中减缓 neu(+)肿瘤生长。我们证明 PTX 和环磷酰胺（CY）联合给药可协同减缓肿瘤生长，并且体外实验表明，在 LPS 成熟前用 PTX 处理 DC 前体可导致共刺激分子表达、IL-12 产生增加，并具有诱导针对 neu(+)肿瘤的具有增强裂解活性的 CD8(+) T 细胞的能力。PTX 处理还可增强从疫苗引流淋巴结分离的 CD11c(+) DC 上的成熟标志物表达。在体外用这些 DC 可激活具有更强裂解能力的 CD8(+) T 细胞，而不是来自单独用疫苗处理的 neu-N 小鼠的 DC。最后，PTX 治疗可导致体内增强抗原特异性、IFN-γ分泌的 CD8(+) T 细胞。因此，用肿瘤疫苗联合使用 PTX 可通过增强 DC 的成熟来改善 T 细胞的启动。
