Intratumoral injection of immature dendritic cells enhances antitumor effect of hyperthermia using magnetic nanoparticles
Intratumoral injection of immature dendritic cells enhances antitumor effect of hyperthermia using magnetic nanoparticles
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DOI：
10.1002/ijc.21061
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发表时间：
2005-09-10
影响因子：
6.4
通讯作者：
Honda, H
中科院分区：
文献类型：
--
作者：
Tanaka, K;Ito, A;Honda, H
树突状细胞（Dendritic cells，DC）是一种有效的抗原呈递细胞，在调节癌症免疫反应中起着关键作用，并且最近被证明可被热休克蛋白（Heat Shock Proteins，HSP）激活。我们以前报道过热疗后热休克蛋白70的表达诱导抗肿瘤免疫。我们的热疗系统使用磁铁矿阳离子脂质体（MCLs）诱导的坏死细胞死亡与热休克蛋白70的释放。在本研究中，我们研究了DC疗法结合MCL诱导的热疗对小鼠黑色素瘤的治疗效果。在体外研究中，当未成熟的DC用在43 ℃加热的小鼠B16黑素瘤细胞脉冲时，DC中的主要组织相容性复合物（MHC）I/II类、共刺激分子CD 80/CD 86和CCR 7上调，从而导致DC成熟。携带黑色素瘤结节的C57 BL/6小鼠通过使用MCL的肿瘤特异性热疗和直接注射的未成熟DC在体内进行使用热疗和DC免疫疗法的组合疗法。将小鼠分为4组：I组（对照）、11组（热疗）、III组（DC治疗）和IV组（热疗+ DC治疗）。在第IV组中60%的小鼠中观察到肿瘤完全消退，而在其他组中的小鼠中未观察到肿瘤消退。联合治疗组小鼠脾细胞体外细胞毒性试验显示，治疗组小鼠的细胞毒性T淋巴细胞（CTL）和自然杀伤细胞（NK）活性明显增强，治疗组小鼠对B16黑色素瘤细胞的第二次攻击产生了排斥反应。本研究为MCL诱导的热疗联合DC治疗晚期恶性肿瘤提供了新的治疗方法。(c)2005 Wiley-Liss，Inc.
Dendritic cells (DCs) are potent antigen-presenting cells that play a pivotal role in regulating immune responses in cancer and have recently been shown to be activated by heat shock proteins (HSPs). We previously reported that HSP70 expression after hyperthermia induces antitumor immunity. Our hyperthermia system using magnetite cationic liposomes (MCLs) induced necrotic cell death that was correlated with HSP70 release. In the present study, we investigated the therapeutic effects of DC therapy combined with MCL-induced hyperthermia on mouse melanoma. In an in vitro study, when immature DCs were pulsed with mouse B16 melanoma cells heated at 43 degrees C, major histocompatibility complex (MHC) class I/II, costimulatory molecules CD80/CD86 and CCR7 in the DCs were upregulated, thus resulting in DC maturation. C57BL/6 mice bearing a melanoma nodule were subjected to combination therapy using hyperthermia and DC immunotherapy in vivo by means of tumor-specific hyperthermia using MCLs and directly injected immature DCs. Mice were divided into 4 groups: group I (control), group 11 (hyperthermia), group III (DC therapy) and group IV (hyperthermia + DC therapy). Complete regression of tumors was observed in 60% of mice in group IV, while no tumor regression was seen among mice in the other groups. Increased cytotoxic T lymphocyte (CTL) and natural killer (NK) activity was observed on in vitro cytotoxicity assay using splenocytes in the cured mice treated with combination therapy, and the cured mice rejected a second challenge of B16 melanoma cells. This study has important implications for the application of MCL-induced hyperthermia plus DC therapy in patients with advanced malignancies as a novel cancer therapy. (c) 2005 Wiley-Liss, Inc.