Inhibition of prostate cancer growth by immunization with a GM-CSF-modified mouse prostate cancer RM-1 cell vaccine in a novel murine model
Inhibition of prostate cancer growth by immunization with a GM-CSF-modified mouse prostate cancer RM-1 cell vaccine in a novel murine model
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DOI：
10.3892/ol.2017.7332
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发表时间：
2018-01-01
期刊：
影响因子：
2.9
通讯作者：
Yin, Weihua
中科院分区：
文献类型：
--
作者：
Xia, Hongmei;Luo, Xiaojing;Yin, Weihua
由于缺乏破坏免疫耐受的有效方法，晚期前列腺癌很难治疗。植入活 RM-1 细胞的 C57BL/6 雄性和雌性小鼠代表了一种新型晚期前列腺癌小鼠模型，用于研究用粒细胞巨噬细胞集落刺激因子 (GM-CSF) 修饰的 RM-1 细胞疫苗免疫后的抗肿瘤效果，这已在之前描述过。进行体外细胞毒活性和细胞因子分泌实验以研究抗肿瘤反应。针对 RM-1 细胞免疫的雌性小鼠脾细胞的细胞毒性特征主要涉及细胞毒性 T 淋巴细胞 (CTL) 裂解，以及较小程度的自然杀伤 (NK) 细胞裂解。在男性中也观察到 NK 细胞裂解，但没有表现出 CTL 裂解的证据。与其他组相比，GM-CSF修饰细胞疫苗组的干扰素-γ分泌显着增加。 IL-4 水平较低。为了进一步研究抗肿瘤免疫反应，对接受 GM-CSF 修饰的 RM-1 细胞疫苗的雌性小鼠的脾脏和肿瘤中的分化簇 4 (CD4)T 细胞和 CD8 T 细胞进行了分析。与雌性小鼠不同，雄性小鼠脾脏中的 NK 细胞比例最高。在任何组的肿瘤组织中均未检测到 NK 细胞。性别之间的差异可以解释免疫反应的特异性，因为女性对前列腺抗原不耐受，而男性则不能。该模型具有临床意义，因为它可以转化为人类免疫学，并为研究前列腺癌的免疫疗法提供了一种有效且方便的方法。
Advanced prostate cancer is difficult to treat owing to a lack of effective approaches for disrupting immune tolerance. C57BL/6 male and female mice implanted with viable RM-1 cells represent a novel murine model of advanced prostate cancer for studying antitumor effects following immunization with a granulocyte-macrophage colony-stimulating factor (GM-CSF)-modified RM-1 cell vaccine, which has been described previously. In vitro cytotoxic activity and cytokine secretion experiments were conducted to investigate the antitumor response. The cytotoxicity profile of splenocytes from female mice immunized against RM-1 cells primarily involved cytotoxic T lymphocyte (CTL) lysis and, to a lesser extent, natural killer (NK) cell lysis. NK cell lysis was also observed in males, which exhibited no evidence of CTL lysis. The secretion of interferon-gamma in the GM-CSF-modified cell vaccine group was significantly increased compared with the other groups. The level of interleukin-4 was low. To investigate the antitumor immune response further, cluster of differentiation 4 (CD4)T cells and CD8 T cells were analyzed in the spleens and tumors of female mice receiving the GM-CSF-modified RM-1 cell vaccine. Unlike female mice, males exhibited the highest proportion of NK cells in the spleen. NK cells were not detected in the tumor tissue in any of the groups. The difference between the sexes may explain the specificity of the immune response, as females are intolerant to prostate antigens whereas males are. This model is clinically relevant as it translates to human immunology and offers an effective and convenient method for studying immunotherapy for prostate cancer.