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:Finding potential targets in cell-based immunotherapy for handling the challenges of acute myeloid leukemia.
Finding potential targets in cell-based immunotherapy for handling the challenges of acute myeloid leukemia.
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尽管近期治疗已有进展,急性髓系白血病(AML)仍是一种侵袭性血液系统恶性肿瘤,复发风险高且长期生存率低。为应对这一未满足的临床需求,新型细胞免疫疗法已成为改善抗肿瘤免疫和患者结局的有前景方法。本综述详细考察 AML 细胞免疫疗法的最新进展,包括嵌合抗原受体(CAR)T 细胞治疗、T 细胞受体(TCR)工程化 T 细胞治疗和自然杀伤(NK)细胞疗法。我们批判性评估这些疗法各自的作用机制、当前挑战,以及改善其疗效和安全性的演进策略。综述强调这些前沿免疫策略在克服 AML 固有复杂性和异质性方面的前景。我们讨论最佳靶抗原的识别、减轻靶向脱瘤毒性的重要性,以及增强工程化免疫效应细胞持久性和功能的必要性。总体而言,本综述全面概述了迅速发展的 AML 细胞免疫治疗领域,强调已取得的重大进展,以及将这些创新方法转化为更有效、持久治疗方案的持续努力。
Acute myeloid leukemia (AML) is a hostile hematological malignancy under great danger of relapse and poor long-term survival rates, despite recent therapeutic advancements. To deal with this unfulfilled clinical necessity, innovative cell-based immunotherapies have surfaced as promising approaches to improve anti-tumor immunity and enhance patient outcomes.
In this comprehensive review, we provide a detailed examination of the latest developments in cell-based immunotherapies for AML, including chimeric antigen receptor (CAR) T-cell therapy, T-cell receptor (TCR)-engineered T-cell therapy, and natural killer (NK) cell-based therapies.
We critically evaluate the unique mechanisms of action, current challenges, and evolving strategies to improve the efficacy and safety of these modalities. The review emphasizes how promising these cutting-edge immune-based strategies are in overcoming the inherent complexities and heterogeneity of AML.
We discuss the identification of optimal target antigens, the importance of mitigating on-target/off-tumor toxicity, and the need to enhance the persistence and functionality of engineered immune effector cells. All things considered, this review offers a thorough overview of the rapidly evolving field of cell-based immunotherapy for AML, underscoring the significant progress made and the ongoing efforts to translate these innovative approaches into more effective and durable treatments for this devastating disease.
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