Yano Yutaro, Ueda Yuji, Itoh Tsuyohi, Fuji Nobuaki, Okugawa Kaori, Naito Kei, Imura Kenichiro, Kohara Junji, Hayashi Takashi, Nakane Kazuki, Matsuura Yuko, Kawai Keiichi, Yamagishi Hisakazu
Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kyoto 602-8566, Japan.
Oncol Rep. 2006 Jul;16(1):147-52.
Among a variety of antigen presenting cells (APCs), accumulating results support that the mature dendritic cell (DC) has the potential to induce efficient cytotoxic T lymphocyte (CTL) responses in the context of peptide-based immunotherapy. DCs have been known to assume the mature form by signaling through the CD40-CD40 ligand (CD40L) interaction, which may be provided by activated CD4+ T cells expressing abundant CD40L molecules on their surfaces. Here, we report that DCs generated from peripheral blood monocytes obtained from patients with advanced cancer exhibit a mature phenotype after co-culturing with autologous lymphokine-activated killer (LAK) cells generated by the stimulation of peripheral blood mononuclear cells with anti-CD3 monoclonal antibody (mAb) and interleukin (IL)-2. Part of this process appeared to be dependent on the expression of CD40L on the surface of LAK cells, although it was also suggested that some other humoral factors produced by LAK cells may be involved in this effect as well. DCs derived from the donors, of which LAK cells demonstrated a higher Th1/Th2 ratio upon activation determined by the intracellular detection of interferon-gamma and IL-4, showed more efficient maturation upon co-culture with LAK cells than DCs from donors with a low Th1/Th2 ratio. Importantly, these matured DCs induced a two-times stronger antigen-presenting capacity measured by an allo-reactive mixed lymphocytes reaction assay as compared to immature DCs. These results imply the use of the combination of DCs and LAK cells for immunotherapy against cancer.
在多种抗原呈递细胞（APC）中，越来越多的研究结果表明，在基于肽的免疫治疗中，成熟的树突状细胞（DC）有潜力诱导高效的细胞毒性T淋巴细胞（CTL）反应。已知DC通过CD40- CD40配体（CD40L）相互作用发出信号而呈现成熟形式，这种相互作用可能由在其表面表达丰富CD40L分子的活化CD4 + T细胞提供。在此，我们报告，从晚期癌症患者外周血单核细胞产生的DC，在与通过用抗CD3单克隆抗体（mAb）和白细胞介素（IL）-2刺激外周血单核细胞而产生的自体淋巴因子激活的杀伤细胞（LAK）共培养后，呈现成熟表型。尽管也有人提出LAK细胞产生的一些其他体液因子可能也参与了这种效应，但这一过程的部分似乎依赖于LAK细胞表面CD40L的表达。来自供体的DC，其LAK细胞在通过细胞内检测干扰素-γ和IL-4确定的激活后表现出较高的Th1 / Th2比率，与来自Th1 / Th2比率低的供体的DC相比，与LAK细胞共培养时显示出更有效的成熟。重要的是，通过同种异体反应性混合淋巴细胞反应测定法测量，这些成熟的DC诱导的抗原呈递能力比未成熟的DC强两倍。这些结果暗示了DC和LAK细胞联合用于癌症免疫治疗的可能性。
