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

用表达 α-Gal 表位的结肠直肠癌细胞裂解物脉冲的树突状细胞诱导的细胞毒性 T 淋巴细胞增强抗肿瘤作用

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

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 in vitro. The results demonstrated that DCs pulsed with α-gal-expressing tumor lysate can increase the frequency of CD3+CD8+ 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.

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