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表达α-Gal表位的结肠癌细胞裂解物脉冲树突状细胞诱导的细胞毒性T淋巴细胞的抗肿瘤作用增强。

Enhanced antitumor effect of cytotoxic T lymphocytes induced by dendritic cells pulsed with colorectal cancer cell lysate expressing α-Gal epitopes.

作者信息

Xing Xiaowei, Zou Zhenyu, He Changzheng, Hu Zilong, Liang Kai, Liang Wentao, Wang Yufeng, Du Xiaohui

机构信息

Department of General Surgery, Chinese People's Liberation Army General Hospital, Beijing 100853, P.R. China.

Department of Hernia and Abdominal Wall Surgery, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100853, P.R. China.

出版信息

Oncol Lett. 2019 Jul;18(1):864-871. doi: 10.3892/ol.2019.10376. Epub 2019 May 20.

DOI:10.3892/ol.2019.10376
PMID:31289564
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6546984/
Abstract

Colorectal cancer (CRC) is one of the most common types of gastrointestinal malignancy. Traditional therapeutic options for CRC exhibit a limited effect. Adoptive cellular therapy has emerged as a new treatment strategy for CRC. Dendritic cells (DCs) are potent antigen-presenting cells. Specific cytotoxic T lymphocytes (CTLs) activated by DCs pulsed with tumor lysate have been reported to be a safe and promising treatment approach for CRC. However, the antitumor effect of specific CTLs remains limited. The low immunogenicity of tumor-associated antigens (TAAs) is the main reason for this limited therapeutic effect. In the present study, α-gal epitopes were synthesized on the CRC cell line SW620 to increase the immunogenicity of TAAs. DCs were pulsed with α-gal-expressing tumor lysate and CTLs were activated by these DCs. The cytotoxicity of CTLs was measured . The results demonstrated that DCs pulsed with α-gal-expressing tumor lysate can increase the frequency of CD3CD8 CTLs and natural killer T cells, increase the level of tumor necrosis factor-α produced by CTLs and enhance the cytotoxicity of CTLs against tumor cells. Therefore, this novel approach may be an effective treatment strategy for patients with CRC.

摘要

结直肠癌(CRC)是最常见的胃肠道恶性肿瘤类型之一。CRC的传统治疗方案效果有限。过继性细胞疗法已成为CRC的一种新治疗策略。树突状细胞(DCs)是高效的抗原呈递细胞。据报道,用肿瘤裂解物脉冲处理的DCs激活的特异性细胞毒性T淋巴细胞(CTLs)是一种安全且有前景的CRC治疗方法。然而,特异性CTLs的抗肿瘤作用仍然有限。肿瘤相关抗原(TAAs)的低免疫原性是这种治疗效果有限的主要原因。在本研究中,在CRC细胞系SW620上合成了α - 半乳糖表位以提高TAAs的免疫原性。用表达α - 半乳糖的肿瘤裂解物脉冲处理DCs,并通过这些DCs激活CTLs。检测了CTLs的细胞毒性。结果表明,用表达α - 半乳糖的肿瘤裂解物脉冲处理的DCs可增加CD3CD8 CTLs和自然杀伤T细胞的频率,提高CTLs产生的肿瘤坏死因子 - α水平,并增强CTLs对肿瘤细胞的细胞毒性。因此,这种新方法可能是CRC患者的一种有效治疗策略。

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