Fu Changhao, Zhou Ning, Zhao Yuanyuan, Duan Jinyue, Xu Hao, Wang Yi
Department of Regenerative Medicine, School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China.
Oncol Lett. 2019 Dec;18(6):5897-5904. doi: 10.3892/ol.2019.10952. Epub 2019 Oct 2.
Increasing evidence supports the concept that cancer stem cells (CSCs) are responsible for cancer progression and metastasis, therapy resistance and relapse. In addition to conventional therapies for colon cancer, the development of immunotherapies targeting cancer stem cells appears to be a promising strategy to suppress tumor recurrence and metastasis. In the present study, dendritic cells (DCs) were pulsed with whole-tumor cell lysates or total RNA of CD44 colon cancer stem cells (CCSCs) isolated from mouse colon adenocarcinoma CT-26 cell cultures and investigated for their antitumor immunity against CCSCs and . In a model of colon adenocarcinoma using BALB/c mice, a sequential reduction in tumor volume and weight was associated with an extended survival in tumor-bearing mice vaccinated with DCs pulsed with RNA or CCSC lysate. In addition, a lactate dehydrogenase assay indicated that cytotoxic T-cells derived from the treated mice exhibited strong cytotoxic activity. Additionally, an enzyme-linked immunosorbent assay revealed that the cytotoxic T-cells of the treated mice released higher levels of interferon-γ against CCSCs compared with those of the control group. In all experiments, the antitumor efficacy of the lysate-pulsed DC-treated and RNA-pulsed DC-treated groups were significantly higher compared with that of the DC-treated and control groups. The results of the present study indicated the potential use of DCs pulsed with cancer stem cell lysates as a potent therapeutic antigen to target CSCs in colon cancer. Additionally, the results provided a rationale for using lysate-pulsed DCs to eliminate residual tumor deposits in post-operative patients.
越来越多的证据支持这样一种观点，即癌症干细胞（CSCs）与癌症进展、转移、治疗抵抗及复发有关。除了结肠癌的传统疗法外，开发针对癌症干细胞的免疫疗法似乎是抑制肿瘤复发和转移的一种有前景的策略。在本研究中，用从小鼠结肠腺癌CT-26细胞培养物中分离出的CD44结肠癌干细胞（CCSCs）的全肿瘤细胞裂解物或总RNA对树突状细胞（DCs）进行脉冲处理，并研究其针对CCSCs的抗肿瘤免疫。在使用BALB/c小鼠的结肠腺癌模型中，肿瘤体积和重量的持续减少与接种了用RNA或CCSC裂解物脉冲处理的DCs的荷瘤小鼠的生存期延长相关。此外，乳酸脱氢酶测定表明，来自处理过的小鼠的细胞毒性T细胞表现出很强的细胞毒性活性。另外，酶联免疫吸附测定显示，与对照组相比，处理过的小鼠的细胞毒性T细胞针对CCSCs释放出更高水平的干扰素-γ。在所有实验中，裂解物脉冲DC处理组和RNA脉冲DC处理组的抗肿瘤功效均显著高于DC处理组和对照组。本研究结果表明，用癌症干细胞裂解物脉冲处理的DCs有可能作为一种有效的治疗性抗原用于靶向结肠癌中的CSCs。此外，这些结果为使用裂解物脉冲DCs消除术后患者残留的肿瘤沉积物提供了理论依据。
