肿瘤细胞治疗研究
英文原题：Aldehyde Dehydrogenese-1 High Cancer Stem-like Cells/Cancer-initiating Cells Escape from Cytotoxic T Lymphocytes due to Lower Expression of Human Leukocyte Antigen Class 1.
High-36 细胞和 Low-8 细胞分别代表新型胃癌 CSC/CIC 和非 CSC/CIC。
背景/目的：人胃癌干细胞样细胞（CSC）/癌症起始细胞可鉴定为醛脱氢酶高表达（ALDHhigh）细胞。免疫检查点阻断等癌症免疫治疗已获批用于晚期胃癌，但其对胃癌 CSC/癌症起始细胞（CIC）的疗效仍不明确。本研究旨在探讨胃癌 CSC/CIC 对免疫治疗的敏感性。 材料与方法：采用人胃癌细胞系 MKN-45，通过 ALDEFLUOR 实验分选 ALDHhigh 和 ALDHlow 克隆细胞。采用 qRT-PCR 检测 ALDH1A1 表达，并评估成球能力以确认 CSC/CIC 特征。在 ALDHhigh 和 ALDHlow 克隆细胞中过表达模型新抗原 AP2S1，并通过 IFN-γ ELISPOT 试验评估其对 AP2S1 特异性 T 细胞受体工程化 T 细胞（TCR-T）的敏感性。 结果：从 MKN-45 细胞中分离出 3 个 ALDHhigh 克隆。这些细胞在体外培养超过 2 个月仍保持稳定表型。High-36 克隆成球能力最高，Low-8 最低。与 Low-8 相比，High-36 细胞 HLA-A24 表达较低。AP2S1 特异性 TCR-T 对 High-36 细胞的反应低于对 Low-8 细胞的反应。 结论：High-36 和 Low-8 分别代表新型胃癌 CSC/CIC 和非 CSC/CIC。ALDHhigh CSC/CIC 可因 HLA I 类表达较低而逃避免疫 T 细胞。
BACKGROUND/AIM: Human gastric cancer stem-like cells (CSCs)/cancer-initiating cells can be identified as aldehyde dehydrogenase-high (ALDH high ) cells. Cancer immunotherapy employing immune checkpoint blockade has been approved for advanced gastric cancer cases. However, the effectiveness of cancer immunotherapy against gastric CSCs/CICs remains unclear. This study aimed to investigate the susceptibility of gastric CSCs/CICs to immunotherapy. MATERIALS AND METHODS: Gastric CSCs/CICs were isolated as ALDH high cells using the human gastric cancer cell line, MKN-45. ALDH high clone cells and ALDH low clone cells were isolated using the ALDEFLUOR assay. ALDH1A1 expression was assessed via qRT-PCR. Sphere-forming ability was evaluated to confirm the presence of CSCs/CICs. A model neoantigen, AP2S1, was over-expressed in ALDH high clone cells and ALDH low clone cells, and susceptibility to AP2S1-specific TCR-T cells was assessed using IFN ELISPOT assay. RESULTS: Three ALDH high clone cells were isolated from MKN-45 cells. ALDH high clone cells exhibited a stable phenotype in in vitro culture for more than 2 months. The High-36 clone cells demonstrated the highest sphere-forming ability, whereas the Low-8 cells showed the lowest sphere-forming ability. High-36 cells exhibited lower expression of HLA-A24 compared to Low-8 cells. TCR-T cells specific for AP2S1 showed lower reactivity to High-36 cells compared to Low-8 cells. CONCLUSION: High-36 cells and Low-8 cells represent novel gastric CSCs/CICs and non-CSCs/CICs, respectively. ALDH high CSCs/CICs evade T cells due to lower expression of HLA class 1.
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