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急性髓系白血病中的免疫抑制微环境:概述、治疗靶点及相应策略

Immunosuppressive microenvironment in acute myeloid leukemia: overview, therapeutic targets and corresponding strategies.

作者信息

Zha Chenyu, Yang Xinyu, Yang Jun, Zhang Yujie, Huang Rui

机构信息

Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.

The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China.

出版信息

Ann Hematol. 2024 Dec;103(12):4883-4899. doi: 10.1007/s00277-024-06117-9. Epub 2024 Nov 28.

Abstract

Similar to other malignancies, immune dysregulation is a key feature of acute myeloid leukemia (AML), manifesting as suppressed anti-leukemia immune cells, immune evasion by leukemia blasts, and disease progression. Various immunosuppressive factors within the AML microenvironment contribute to the weakening of host immune responses and the efficacy of cellular immunotherapy. To address these challenges, strategies targeting immunosuppressive elements within the AML microenvironment aim to bolster host or adoptive immune effector cells, ultimately enhancing leukemia treatment. Additionally, the off-target effects of certain targeted drugs (venetoclax, sorafenib, ivosidenib, etc.) may also positively impact anti-AML immunity and immunotherapy. This review provides an overview of the immunosuppressive factors present in AML microenvironment and the strategies developed to rescue immune cells from immunosuppression. We also outline how targeted agents can alter the immune landscape in AML patients, and discuss the potential of targeted drugs to benefit host anti-leukemia immunity and immunotherapy for AML.

摘要

与其他恶性肿瘤相似,免疫失调是急性髓系白血病(AML)的一个关键特征,表现为抗白血病免疫细胞受到抑制、白血病原始细胞逃避免疫监视以及疾病进展。AML微环境中的各种免疫抑制因子会导致宿主免疫反应减弱以及细胞免疫治疗效果降低。为应对这些挑战,针对AML微环境中免疫抑制成分的策略旨在增强宿主或过继性免疫效应细胞,最终提高白血病治疗效果。此外,某些靶向药物(维奈克拉、索拉非尼、艾伏尼布等)的脱靶效应也可能对AML免疫和免疫治疗产生积极影响。本综述概述了AML微环境中存在的免疫抑制因子以及为使免疫细胞从免疫抑制中恢复而制定的策略。我们还概述了靶向药物如何改变AML患者的免疫格局,并讨论靶向药物对宿主抗白血病免疫和AML免疫治疗产生益处的潜力。

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