Monocyte galactose/N-acetylgalactosamine-specific C-type lectin receptor stimulant immunotherapy of an experimental glioma. Part II: combination with external radiation improves survival.
Monocyte galactose/N-acetylgalactosamine-specific C-type lectin receptor stimulant immunotherapy of an experimental glioma. Part II: combination with external radiation improves survival.
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DOI：
10.2147/cmar.s33355
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发表时间：
2012
影响因子：
3.3
通讯作者：
Preul MC
中科院分区：
文献类型：
--
作者：
Kushchayev SV;Sankar T;Eggink LL;Kushchayeva YS;Wiener PC;Hoober JK;Eschbacher J;Liu R;Shi FD;Abdelwahab MG;Scheck AC;Preul MC
半乳糖/N-乙酰半乳糖胺特异性C型凝集素受体（GCLR）配体的肽模拟物表现出单核细胞刺激活性，但单独应用于同源小鼠恶性神经胶质瘤时并不能延长生存期。在本研究中，研究了 GCLRP 与辐射的联合效应。 C57BL/6 小鼠接受立体定向颅内植入 GL261 神经胶质瘤细胞。第七天通过磁共振成像根据随机肿瘤大小对动物进行分组。一组仅接受颅部放射（第 7 天和第 9 天为 4 Gy）的动物与接受放射和 GCLRP 治疗的动物（第 7 天和第 9 天为 4 Gy，并从第 7 天开始每隔几天皮下注射 1 nmol/g）进行比较。磁共振成像用于评估肿瘤生长并与存活率相关。使用荧光激活细胞分选分析、组织学和酶联免疫吸附测定对血液和脑组织的肿瘤和对侧半球进行分析。 GCLRP 激活外周单核细胞，并与血液中树突状细胞前体细胞的增加有关。与仅放疗组相比，GCLRP + 放疗组的平均生存率增加 (P < 0.001)，肿瘤尺寸更小 (P < 0.02)。肿瘤半球（P < 0.005）和对侧无肿瘤半球（P < 0.01）中树突状细胞的积累与治疗相关。特定的单核细胞来源的脑细胞群与恶性神经胶质瘤建立了重要的关系。 GCLRP与放射组合的生物学效应可能会更成功，因为放射对肿瘤细胞造成损伤，并且GCLRP激活的免疫细胞增强或保留了肿瘤细胞抗原的呈递。单核细胞衍生的脑细胞可能是创建有效免疫方式的重要目标，例如利用本研究中描述的受体系统。
A peptide mimetic of a ligand for the galactose/N-acetylgalactosamine-specific C-type lectin receptors (GCLR) exhibited monocyte-stimulating activity, but did not extend survival when applied alone against a syngeneic murine malignant glioma. In this study, the combined effect of GCLRP with radiation was investigated. C57BL/6 mice underwent stereotactic intracranial implantation of GL261 glioma cells. Animals were grouped based on randomized tumor size by magnetic resonance imaging on day seven. One group that received cranial radiation (4 Gy on days seven and nine) only were compared with animals treated with radiation and GCLRP (4 Gy on days seven and nine combined with subcutaneous injection of 1 nmol/g on alternative days beginning on day seven). Magnetic resonance imaging was used to assess tumor growth and correlated with survival rate. Blood and brain tissues were analyzed with regard to tumor and contralateral hemisphere using fluorescence-activated cell sorting analysis, histology, and enzyme-linked immunosorbent assay. GCLRP activated peripheral monocytes and was associated with increased blood precursors of dendritic cells. Mean survival increased (P < 0.001) and tumor size was smaller (P < 0.02) in the GCLRP + radiation group compared to the radiation-only group. Accumulation of dendritic cells in both the tumoral hemisphere (P < 0.005) and contralateral tumor-free hemisphere (P < 0.01) was associated with treatment. Specific populations of monocyte-derived brain cells develop critical relationships with malignant gliomas. The biological effect of GCLRP in combination with radiation may be more successful because of the damage incurred by tumor cells by radiation and the enhanced or preserved presentation of tumor cell antigens by GCLRP-activated immune cells. Monocyte-derived brain cells may be important targets for creating effective immunological modalities such as employing the receptor system described in this study.