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:Clinical application of cytokine-induced killer cells in cancer immunotherapy.
Clinical application of cytokine-induced killer cells in cancer immunotherapy.
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细胞因子诱导的杀伤(CIK)细胞表现出强效的抗肿瘤活性,对严格MHC相容性的依赖性降低,这由T细胞受体(TCR)依赖性识别和自然杀伤(NK)样、MHC非限制性细胞毒性共同介导。本叙述性综述综合了临床试验评估中的证据,包括48项已发表研究。我们探讨了增强CIK功能的策略,如工程化改造、与检查点抑制剂联合以及与应用树突状细胞共给药。CIK细胞疗法在辅助治疗背景下有效减少治疗后复发,并在晚期疾病中增强化疗结局,显著改善多种癌症的关键生存指标。本文对持续存在的挑战进行了详细分析,如肿瘤微环境中的免疫抑制状态、体内持久性有限、产品变异性以及选择最佳治疗方案。未来转化方面的进展取决于建立标准化生产流程、开发由精准生物标志物指导的治疗算法,并在临床环境中验证下一代工程化CIK细胞产品。
Cytokine-induced killer (CIK) cells exhibit potent antitumor activity with reduced dependence on strict MHC compatibility, mediated by a combination of T-cell receptor (TCR)-dependent recognition and natural killer (NK)-like, MHC-unrestricted cytotoxicity. This narrative review synthesizes evidence from clinical trial evaluations, including 48 published studies.
We examine strategies to enhance CIK function, such as engineering, combination with checkpoint inhibitors, and co-administration with dendritic cells. CIK cell therapy effectively reduces post-treatment recurrence in the adjuvant setting and enhances chemotherapy outcomes in advanced disease, significantly improving key survival metrics across multiple cancers.
A detailed analysis is conducted of ongoing challenges, such as immunosuppressive conditions in tumor microenvironments, limited in vivo durability, product variability, and choosing the best treatment plans. Future advancements in translation depend on establishing standardized manufacturing procedures, developing treatment algorithms guided by precision biomarkers, and validating next-generation engineered CIK cell products in clinical settings.
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