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
英文原题:Generation and assessment of cytokine-induced killer cells for the treatment of colorectal cancer liver metastases.
Generation and assessment of cytokine-induced killer cells for the treatment of colorectal cancer liver metastases.
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结直肠癌(CRC)是全球癌症相关死亡的第二大原因。细胞因子诱导的杀伤(CIK)细胞是一种过继性免疫疗法,据报道在多种癌症中具有强大的抗肿瘤活性。它们是通过在体外将人外周血单个核细胞与细胞因子和单克隆抗体共培养而生成的一种异质性淋巴细胞混合物。
在本研究中,我们探究了从CRC肝转移患者中生成的CIK细胞的产量和功能。我们首先表明,在无血清培养基X-VIVO 15中生成的CIK细胞,与在含10% FBS的RPMI培养基中生成的CIK细胞相比,在CIK培养物中主要细胞亚群的数量和百分比、以及颗粒酶B和穿孔素的细胞内水平、以及促炎细胞因子IL-2、IFN-γ和TNF-α方面均相当。这些CIK细胞对在2D培养或球状体形式下生长的CRC细胞系具有细胞毒性,并且对自体患者来源的肿瘤类器官也具有细胞毒性。供者特征如年龄、性别或既往化疗暴露对CIK细胞数量或功能没有显著影响。这些结果表明,可以从CRC肝转移疾病患者中生成功能性CIK细胞,并支持进一步研究自体CIK细胞在CRC肝转移患者管理中的治疗应用。
Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide. Cytokine-induced killer (CIK) cells are an adoptive immunotherapy reported to have strong anti-tumour activity across a range of cancers. They are a heterogeneous mix of lymphoid cells generated by culturing human peripheral blood mononuclear cells with cytokines and monoclonal antibodies in vitro. In this study, we investigated the yield and function of CIK cells generated from patients with CRC liver metastases.
We first showed that CIK cells generated in serum free medium X-VIVO 15 were comparable to those from RPMI medium with 10% FBS in terms of the number and percentages of the main subsets of cells in the CIK culture, and the intracellular levels of granzyme B and perforin, and the pro-inflammatory cytokines IL-2, IFN-γ and TNF-α. The CIK cells were cytotoxic to CRC cell lines grown in 2D cultures or as spheroids, and against autologous patient-derived tumour organoids.
Donor attributes such as age, sex, or prior chemotherapy exposure had no significant impact on CIK cell numbers or function. These results suggest that functional CIK cells can be generated from patients with CRC liver metastatic disease, and support further investigations into the therapeutic application of autologous CIK cells in the management of patients with CRC liver metastases.
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