RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
细胞因子诱导的杀伤（CIK）细胞对 HCT-15 结直肠癌（CRC）细胞的细胞毒性和细胞因子谱的探索性体外研究
英文原题：An Exploratory in vitro Study of Cytotoxicity and Cytokine Profiling of Cytokine-Induced Killer (CIK) Cells Against HCT-15 Colorectal Cancer (CRC) Cells.
查看英文原题
An Exploratory in vitro Study of Cytotoxicity and Cytokine Profiling of Cytokine-Induced Killer (CIK) Cells Against HCT-15 Colorectal Cancer (CRC) Cells.
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研究概要
这项探索性研究表明，可以从健康个体和 CRC 患者中生成具有功能的 CIK 细胞，并观察到对 HCT-15 细胞的细胞毒活性。这些发现提示了潜在的免疫调节作用，并支持进一步研究 CIK 细胞在联合策略中的应用；然而，仍需更大规模的患者队列和功能验证研究。
研究思路结论见上方概要
背景
细胞因子诱导的杀伤（CIK）细胞因其非主要组织相容性复合体（MHC）限制性细胞毒性而成为一种有前景的过继性免疫疗法。然而，其针对CRC的细胞因子介导反应仍不明确。
方法
在这项探索性研究中，CIK 细胞由三名健康供者和一名转移性 CRC 患者生成。通过流式细胞术评估表型。在多个效靶比（E:T）（1:5 至 40:1）下评估了对 HCT-15 CRC 细胞系的细胞毒性。分别使用来自供者 2 和供者 3 的 CIK 细胞进行了与 5-氟尿嘧啶（5-FU）的联合处理以及使用 105-plex 阵列的细胞因子谱分析。
结果
源自一名CRC患者的CIK细胞表现出与三名健康供者观察范围相当的免疫表型特征（CD3⁺CD8⁺ 85.91%，CD3⁺CD56⁺ 27.81%）。与供者1的CIK细胞共培养后，在较高E:T比下HCT-15活力降低，20:1和40:1时活力分别降至8.98 ± 0.61%和8.08 ± 2.00%。在联合实验中，与供者2的CIK共培养并使用5-FU处理时，20:1 E:T比下HCT-15活力降至1.02 ± 1.01%。使用供者3和CRC患者的CIK细胞观察到类似降低，20:1时分别达到2.60 ± 5.86%和0.0%，两名供者在40:1比下均为0.0%。所有供者的CIK细胞均显示出对HCT-15细胞的剂量依赖性活力降低。供者3 CIK的细胞因子谱分析发现免疫相关因子的变化，包括干扰素γ诱导趋化因子（CXCL9和CXCL10）的上调，以及免疫抑制介质如TIM-3和VEGF的下调。
展开英文摘要原文
BACKGROUND
Cytokine-induced killer (CIK) cells are a promising adoptive immunotherapy due to their non-major histocompatibility complex (MHC)-restricted cytotoxicity. However, their cytokine-mediated response against CRC remains poorly defined.
METHODS
In this exploratory study, CIK cells were generated from three healthy donors and one metastatic CRC patient. Phenotypes were assessed by flow cytometry. Cytotoxicity against the HCT-15 CRC cell line was evaluated at multiple effector-to-target (E:T) ratios (1:5 to 40:1). Combination treatment with 5-fluorouracil (5-FU) and cytokine profiling using a 105-plex array were performed using CIK cells from donor 2 and donor 3, respectively.
RESULTS
CIK cells derived from one CRC patient exhibited phenotypic characteristics (CD3⁺CD8⁺ 85.91%, CD3⁺CD56⁺ 27.81%) comparable to the range observed in three healthy donors. Co-culture with CIK cells from donor 1 resulted in reduced HCT-15 viability at higher E:T ratios, with viability decreasing to 8.98 ± 0.61% and 8.08 ± 2.00% at 20:1 and 40:1, respectively. In combination experiments, HCT-15 viability was reduced to 1.02 ± 1.01% at an E:T ratio of 20:1 when co-cultured with CIK from donor 2 and treated with 5-FU. Similar reductions were observed with CIK cells from donor 3 and the CRC patient, reaching 2.60 ± 5.86% and 0.0% at 20:1, and 0.0% at 40:1 ratio for both donors. CIK cells from all donors showed dose-dependent reduction in cell viability against HCT-15 cells. Cytokine profiling of CIK from donor 3 identified changes in immune-related factors, including upregulation of interferon gamma-inducible chemokines (CXCL9 and CXCL10), alongside downregulation of immunosuppressive mediators such as TIM-3 and VEGF.
CONCLUSION
This exploratory study demonstrates that functional CIK cells can be generated from healthy individuals and CRC patients, with observed cytotoxic activity against HCT-15 cells. The findings suggest potential immunomodulatory effects and support further investigation of CIK cells in combination strategies; however, larger patient cohorts and functional validation studies are required.
论文信息
- 作者
- Chin SP、Nor Arfuzir NN、Kong VW、Cheong SK
- 单位
- Department of Research and Development, Cytopeutics Sdn Bhd, Cyberjaya, Selangor, Malaysia.Malaysia
- 期刊
- ImmunoTargets and therapy2026
- 原文标识
- PubMed 42206240 · DOI 10.2147/ITT.S594441
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