The potential role of the thymus in immunotherapies for acute myeloid leukemia.
The potential role of the thymus in immunotherapies for acute myeloid leukemia.
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DOI：
10.3389/fimmu.2023.1102517
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发表时间：
2023
影响因子：
7.3
通讯作者：
Cao, Huynh
中科院分区：
文献类型：
--
作者：
Hino, Christopher;Xu, Yi;Xiao, Jeffrey;Baylink, David J.;Reeves, Mark E.;Cao, Huynh
关键词：
了解T淋巴细胞免疫的形成因素对于未来恶性血液病免疫治疗策略的发展和应用至关重要。胸腺是一种特殊的中枢淋巴器官，在人类婴儿和青少年阶段产生多样化的T淋巴细胞库中起着重要作用。然而，年龄相关的胸腺退化和疾病或治疗相关的损伤导致其在维持T细胞介导的抗肿瘤/病毒免疫中的持续作用下降。急性髓性白血病（AML）是一种侵袭性血液系统恶性肿瘤，主要影响老年人，并且已知该疾病的进展包括免疫监视受损，包括幼稚T细胞输出减少，T细胞受体库限制和调节性T细胞频率增加。作为迄今为止针对恶性肿瘤开发的最成功的免疫疗法之一，基于T细胞的过继细胞疗法对于开发持久有效的治疗以消除残留的白血病细胞（原始细胞）并预防AML复发至关重要。因此，一个详细的细胞和分子景观如何成人胸腺功能的AML微环境的背景下，将提供新的见解免疫相关的发病机制和再生的功能免疫系统对白血病的AML患者。在此，我们回顾现有的证据支持胸腺功能障碍和T淋巴细胞损伤与AML（II-VI）的个体发生之间的潜在相关性。然后，我们讨论了胸腺如何影响AML（VII）当前和未来的治疗方法。最后，我们回顾了各种策略，以振兴胸腺功能，以提高癌症免疫治疗的精度和疗效（VIII）。
Understanding the factors which shape T-lymphocyte immunity is critical for the development and application of future immunotherapeutic strategies in treating hematological malignancies. The thymus, a specialized central lymphoid organ, plays important roles in generating a diverse T lymphocyte repertoire during the infantile and juvenile stages of humans. However, age-associated thymic involution and diseases or treatment associated injury result in a decline in its continuous role in the maintenance of T cell-mediated anti-tumor/virus immunity. Acute myeloid leukemia (AML) is an aggressive hematologic malignancy that mainly affects older adults, and the disease’s progression is known to consist of an impaired immune surveillance including a reduction in naïve T cell output, a restriction in T cell receptor repertoire, and an increase in frequencies of regulatory T cells. As one of the most successful immunotherapies thus far developed for malignancy, T-cell-based adoptive cell therapies could be essential for the development of a durable effective treatment to eliminate residue leukemic cells (blasts) and prevent AML relapse. Thus, a detailed cellular and molecular landscape of how the adult thymus functions within the context of the AML microenvironment will provide new insights into both the immune-related pathogenesis and the regeneration of a functional immune system against leukemia in AML patients. Herein, we review the available evidence supporting the potential correlation between thymic dysfunction and T-lymphocyte impairment with the ontogeny of AML (II-VI). We then discuss how the thymus could impact current and future therapeutic approaches in AML (VII). Finally, we review various strategies to rejuvenate thymic function to improve the precision and efficacy of cancer immunotherapy (VIII).
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7.3
作者：
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Krummel MF